Autophagy modulators from traditional Chinese medicine: Mechanisms and therapeutic potentials for cancer and neurodegenerative diseases

Journal of Ethnopharmacology

Volumn 194, Issue , 2016, Pages 861-876

  Wang, Sheng Fang ^a   Wu, Ming Yue ^a   Cai, Cui Zan ^a   Li, Min ^b   Lu, Jia Hong ^a  

^a University of Macau   (Macao)

^b HONG KONG BAPTIST UNIVERSITY   (Hong Kong)

Author keywords

Autophagy; Cancer; Neurodegenerative diseases; TCM

Indexed keywords

HERBACEOUS AGENT;

ALZHEIMER DISEASE; ANTIGEN PRESENTATION; ATHEROSCLEROSIS; AUTOLYSOSOME; AUTOPHAGOSOME; AUTOPHAGY; BIBLIOGRAPHIC DATABASE; BREAST CANCER; CANCER GROWTH; CARCINOGENESIS; CARDIOMYOPATHY; CELL MATURATION; CELL PROLIFERATION; CEREBROVASCULAR ACCIDENT; CHINESE MEDICINE; DEGENERATIVE DISEASE; HOST RESISTANCE; HUMAN; HUNTINGTON CHOREA; HYPERTENSION; IMMUNOPATHOLOGY; IMMUNOSURVEILLANCE; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER; LYSOSOME; NEOPLASM; NONHUMAN; PARKINSON DISEASE; REVIEW; UPREGULATION; DRUG EFFECTS; ETHNOPHARMACOLOGY; NEOPLASMS; NEURODEGENERATIVE DISEASES; PHYTOTHERAPY; PROCEDURES;

AUTOPHAGY; DRUGS, CHINESE HERBAL; ETHNOPHARMACOLOGY; HUMANS; MEDICINE, CHINESE TRADITIONAL; NEOPLASMS; NEURODEGENERATIVE DISEASES; PHYTOTHERAPY;

EID: 85003956486     PISSN: 03788741     EISSN: 18727573     Source Type: Journal    
DOI: 10.1016/j.jep.2016.10.069     Document Type: Review

References (243)

1. Abe, A., Yamada, H., Moriya, S., Miyazawa, K., The. BETA.-Carboline Alkaloid Harmol Induces Cell Death via Autophagy but Not Apoptosis in Human Non-small Cell Lung Cancer A549 Cells. Biol. Pharm. Bull. 34:8 (2011), 1264–1272.
2. Abedin, M., Wang, D., McDonnell, M., Lehmann, U., Kelekar, A., Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death Differ. 14:3 (2007), 500–510.
3. Adams, M., Kunert, O., Haslinger, E., Bauer, R., Inhibition of leukotriene biosynthesis by quinolone alkaloids from the fruits of Evodia rutaecarpa. Planta Med. 70 (2004), 904–908.
4. Adhami, F., Schloemer, A., Kuan, C.-Y., The roles of autophagy in cerebral ischemia. Autophagy 3:1 (2007), 42–44.
5. Adi‐Harel, S., Erlich, S., Schmukler, E., Cohen‐Kedar, S., Segev, O., Mizrachy, L., Hirsch, J.A., Pinkas‐Kramarski, R., Beclin 1 self‐association is independent of autophagy induction by amino acid deprivation and rapamycin treatment. J. Cell. Biochem. 110:5 (2010), 1262–1271.
6. Aguib, Y., Heiseke, A., Gilch, S., Riemer, C., Baier, M., Ertmer, A., Schätzl, H.M., Autophagy induction by trehalose counter-acts cellular prion-infection. Autophagy 5:3 (2009), 361–369.
7. Ait-Mohamed, O., Battisti, V., Joliot, V., Fritsch, L., Pontis, J., Medjkane, S., Redeuilh, C., Lamouri, A., Fahy, C., Rholam, M., Acetonic extract of Buxus sempervirens induces cell cycle arrest, apoptosis and autophagy in breast cancer cells. Plos One, 6(9), 2011, e24537.
8. Alarcón de la Lastra, C., Villegas, I., Resveratrol as an anti‐inflammatory and anti‐aging agent: mechanisms and clinical implications. Mol. Nutr. Food Res. 49:5 (2005), 405–430.
9. Ali, B.H., Blunden, G., Tanira, M.O., Nemmar, A., Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem. Toxicol. 46:2 (2008), 409–420.
10. Arel-Dubeau, A.-M., Longpré, F., Bournival, J., Tremblay, C., Demers-Lamarche, J., Haskova, P., Attard, E., Germain, M., Martinoli, M.-G., Cucurbitacin E Has neuroprotective properties and autophagic modulating activities on dopaminergic neurons. Oxid. Med. Cell Longev., 2014, 2014.
11. Bae, N., Ahn, T., Chung, S., Oh, M.S., Ko, H., Oh, H., Park, G., Yang, H.O., The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in models of Parkinson's disease. J. Ethnopharmacol. 134:2 (2011), 313–322.
12. Borek, C., Antioxidant health effects of aged garlic extract. J. Nutr. 131:3 (2001), 1010S–1015S.
13. Cao, B.-Y., Yang, Y.-P., Luo, W.-F., Mao, C.-J., Han, R., Sun, X., Cheng, J., Liu, C.-F., Paeoniflorin, a potent natural compound, protects PC12 cells from MPP+ and acidic damage via autophagic pathway. J. Ethnopharmacol. 131:1 (2010), 122–129.
14. Carneiro, L.A., Travassos, L.H., The interplay between NLRs and autophagy in immunity and inflammation. Front. Immunol., 2013, 4.
15. Chakraborty, D., Bishayee, K., Ghosh, S., Biswas, R., Mandal, S.K., Khuda-Bukhsh, A.R., [6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: drug–DNA interaction and expression of certain signal genes in HeLa cells. Eur. J. Pharmacol. 694:1 (2012), 20–29.
16. Chang, K.H., Yan, M.D., Yao, C.J., Lin, P.C., Lai, G.M., Honokiol‑induced apoptosis and autophagy in glioblastoma multiforme cells. Oncol. Lett. 6:5 (2013), 1435–1438.
17. Chea, A., Hout, S., Bun, S.-S., Tabatadze, N., Gasquet, M., Azas, N., Elias, R., Balansard, G., Antimalarial activity of alkaloids isolated from Stephania rotunda. J. Ethnopharmacol. 112:1 (2007), 132–137.
18. Chen, B.J., Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F. Leuk. Lymphoma 42:3 (2001), 253–265.
19. Chen, J.-J., Long, Z.-J., Xu, D.-F., Xiao, R.-Z., Liu, L.-L., Xu, Z.-F., Qiu, S.X., Lin, D.-J., Liu, Q., Inhibition of autophagy augments the anticancer activity of α-mangostin in chronic myeloid leukemia cells. Leuk. Lymphoma 55:3 (2014), 628–638.
20. Chen, L.-L., Song, J.-X., Lu, J.-H., Yuan, Z.-W., Liu, L.-F., Durairajan, S.S.K., Li, M., Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway. J. Neuroimmune. Pharm. 9:3 (2014), 380–387.
21. Chen, M., Du, Y., Qui, M., Wang, M., Chen, K., Huang, Z., Jiang, M., Xiong, F., Chen, J., Zhou, J., Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway. Oncol. Rep. 29:2 (2013), 430–436.
22. Chen, S., Zhang, X., Song, L., Le, W., Autophagy dysregulation in amyotrophic lateral sclerosis. Brain Pathol. 22:1 (2012), 110–116.
23. Cheung, Z.H., Ip, N.Y., Autophagy deregulation in neurodegenerative diseases–recent advances and future perspectives. J. Neurochem. 118:3 (2011), 317–325.
24. Chiang, L.-C., Ng, L.T., Liu, L.-T., Shieh, D.-e., Lin, C.-C., Cytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species. Planta Med. 69:8 (2003), 705–709.
25. Choi, A.M., Ryter, S.W., Levine, B., Autophagy in human health and disease. N. Engl. J. Med. 368:7 (2013), 651–662.
26. Chow, S.E., Chen, Y.W., Liang, C.A., Huang, Y.K., Wang, J.S., Wogonin induces cross‐regulation between autophagy and apoptosis via a variety of Akt pathway in human nasopharyngeal carcinoma cells. J. Cell. Biochem. 113:11 (2012), 3476–3485.
27. Chu, Y.-L., Ho, C.-T., Chung, J.-G., Rajasekaran, R., Sheen, L.-Y., Allicin induces p53-mediated autophagy in Hep G2 human liver cancer cells. J. Agric. Food Chem. 60:34 (2012), 8363–8371.
28. Cordell, G.A., Quinn‐Beattie, M.L., Farnsworth, N.R., The potential of alkaloids in drug discovery. Phytother. Res. 15:3 (2001), 183–205.
29. Crews, L., Spencer, B., Desplats, P., Patrick, C., Paulino, A., Rockenstein, E., Hansen, L., Adame, A., Galasko, D., Masliah, E., Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of α-synucleinopathy. PloS One, 5(2), 2010, e9313.
30. Crotzer, V.L., Blum, J.S., Autophagy and its role in MHC-mediated antigen presentation. J. Immunol. 182:6 (2009), 3335–3341.
31. Cullup, T., Kho, A.L., Dionisi-Vici, C., Brandmeier, B., Smith, F., Urry, Z., Simpson, M.A., Yau, S., Bertini, E., McClelland, V., Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. Nat. Genet. 45:1 (2013), 83–87.
32. D'Amelio, M., Cecconi, F., A novel player in the p53-mediated autophagy: sestrin2. Cell Cycle 8:10 (2009), 1466–1470.
33. Dai, Z.-j., Gao, J., Ji, Z.-z., Wang, X.-j., Ren, H.-t., Liu, X.-x., Wu, W.-y., Kang, H.-f., Guan, H.-t., Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3. J. Ethnopharmacol. 123:1 (2009), 91–96.
34. De Meyer, G.R., Martinet, W., Autophagy in the cardiovascular system. BBA Mol. Cell Res. 1793:9 (2009), 1485–1495.
35. Decressac, M., Mattsson, B., Weikop, P., Lundblad, M., Jakobsson, J., Björklund, A., TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity. Proc. Natl. Acad. Sci. 110:19 (2013), E1817–E1826.
36. Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D., Chen, G., Mukherjee, C., Shi, Y., Gélinas, C., Fan, Y., Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10:1 (2006), 51–64.
37. Deng, Y.-N., Shi, J., Liu, J., Qu, Q.-M., Celastrol protects human neuroblastoma SH-SY5Y cells from rotenone-induced injury through induction of autophagy. Neurochem. Int. 63:1 (2013), 1–9.
38. Du, B., Zhang, Z., Li, N., Madecassoside prevents Aβ 25–35-induced inflammatory responses and autophagy in neuronal cells through the class III PI3K/Beclin-1/Bcl-2 pathway. Int. Immunophamacol. 20:1 (2014), 221–228.
39. Durairajan, S.S.K., Huang, Y., Chen, L., Song, J., Liu, L., Li, M., Corynoxine isomers decrease levels of amyloid-β peptide and amyloid-β precursor protein by promoting autophagy and lysosome biogenesis. Mol. Neurodegener. 8:1 (2013), 1–2.
40. Duran, A., Linares, J.F., Galvez, A.S., Wikenheiser, K., Flores, J.M., Diaz-Meco, M.T., Moscat, J., The signaling adaptor p62 is an important NF-κB mediator in tumorigenesis. Cancer Cell 13:4 (2008), 343–354.
41. Egan, D.F., Shackelford, D.B., Mihaylova, M.M., Gelino, S., Kohnz, R.A., Mair, W., Vasquez, D.S., Joshi, A., Gwinn, D.M., Taylor, R., Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331:6016 (2011), 456–461.
42. Erlich, S., Mizrachy, L., Segev, O., Lindenboim, L., Zmira, O., Adi-Harel, S., Hirsch, J.A., Stein, R., Pinkas-Kramarski, R., Differential interactions between Beclin 1 and Bcl-2 family members. Autophagy 3:6 (2007), 561–568.
43. Feng, Z., Zhang, H., Levine, A.J., Jin, S., The coordinate regulation of the p53 and mTOR pathways in cells. P. Natl. Acad. Sci. USA 102:23 (2005), 8204–8209.
44. Filomeni, G., Desideri, E., Cardaci, S., Graziani, I., Piccirillo, S., Rotilio, G., Ciriolo, M.R., Carcinoma cells activate AMP-activated protein kinase-dependent autophagy as survival response to kaempferol-mediated energetic impairment. Autophagy 6:2 (2010), 202–216.
45. Fujita, N., Itoh, T., Omori, H., Fukuda, M., Noda, T., Yoshimori, T., The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol. Biol. Cell 19:5 (2008), 2092–2100.
46. Fujiwara, M., Marusawa, H., Wang, H., Iwai, A., Ikeuchi, K., Imai, Y., Kataoka, A., Nukina, N., Takahashi, R., Chiba, T., Parkin as a tumor suppressor gene for hepatocellular carcinoma. Oncogene 27:46 (2008), 6002–6011.
47. Fung, C., Lock, R., Gao, S., Salas, E., Debnath, J., Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol. Biol. Cell 19:3 (2008), 797–806.
48. Furuya, N., Yu, J., Byfield, M., Pattingre, S., Levine, B., The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy, and tumor suppressor function. Autophagy 1:1 (2005), 46–52.
49. Geisler, S., Holmström, K.M., Skujat, D., Fiesel, F.C., Rothfuss, O.C., Kahle, P.J., Springer, W., PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 12:2 (2010), 119–131.
50. Geisler, S., Holmström, K.M., Treis, A., Skujat, D., Weber, S.S., Fiesel, F.C., Kahle, P.J., Springer, W., The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations. Autophagy 6:7 (2010), 871–878.
51. Geng, J., Klionsky, D.J., The Atg8 and Atg12 ubiquitin‐like conjugation systems in macroautophagy. EMBO Rep. 9:9 (2008), 859–864.
52. Gewirtz, D.A., Autophagy, senescence and tumor dormancy in cancer therapy. Autophagy 5:8 (2009), 1232–1234.
53. Gibbons, S., Plants as a source of bacterial resistance modulators and anti-infective agents. Phytochem. Rev. 4:1 (2005), 63–78.
54. Giordano, S., Darley-Usmar, V., Zhang, J., Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease. Redox Biol. 2 (2014), 82–90.
55. Gleason, C.E., Lu, D., Witters, L.A., Newgard, C.B., Birnbaum, M.J., The role of AMPK and mTOR in nutrient sensing in pancreatic β-cells. J. Biol. Chem. 282:14 (2007), 10341–10351.
56. Goedert, M., Clavaguera, F., Tolnay, M., The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci. 33:7 (2010), 317–325.
57. Griffin, C., McNulty, J., Pandey, S., Pancratistatin induces apoptosis and autophagy in metastatic prostate cancer cells. Int. J. Oncol. 38:6 (2011), 1549–1556.
58. Guertin, D.A., Sabatini, D.M., Defining the role of mTOR in cancer. Cancer Cell 12:1 (2007), 9–22.
59. Guo, J., Chang, L., Zhang, X., Pei, S., Yu, M., Gao, J., Ginsenoside compound K promotes β‑amyloid peptide clearance in primary astrocytes via autophagy enhancement. Exp. Ther. Med. 8:4 (2014), 1271–1274.
60. Guo, J.Y., Chen, H.-Y., Mathew, R., Fan, J., Strohecker, A.M., Karsli-Uzunbas, G., Kamphorst, J.J., Chen, G., Lemons, J.M., Karantza, V., Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Gene. Dev. 25:5 (2011), 460–470.
61. Guo, J.Y., Karsli-Uzunbas, G., Mathew, R., Aisner, S.C., Kamphorst, J.J., Strohecker, A.M., Chen, G., Price, S., Lu, W., Teng, X., Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Gene. Dev. 27:13 (2013), 1447–1461.
62. Guo, J.Y., Xia, B., White, E., Autophagy-mediated tumor promotion. Cell 155:6 (2013), 1216–1219.
63. Han, H.-Y., Park, B.-S., Lee, G.S., Jeong, S.-H., Kim, H., Ryu, M.H., Autophagic cell death by Poncirus trifoliata Rafin., a traditional oriental medicine, in human oral cancer HSC-4 cells. Evid. Based Compl. Alt., 2015, 2015.
64. Hanada, T., Noda, N.N., Satomi, Y., Ichimura, Y., Fujioka, Y., Takao, T., Inagaki, F., Ohsumi, Y., The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J. Biol. Chem. 282:52 (2007), 37298–37302.
65. Hao, D., Ma, P., Mu, J., Chen, S., Xiao, P., Peng, Y., Huo, L., Xu, L., Sun, C., De novo characterization of the root transcriptome of a traditional Chinese medicinal plant Polygonum cuspidatum. Sci. China Life Sci. 55:5 (2012), 452–466.
66. Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:7095 (2006), 885–889.
67. Hara, T., Takamura, A., Kishi, C., Iemura, S.-i., Natsume, T., Guan, J.-L., Mizushima, N., FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J. Cell Biol. 181:3 (2008), 497–510.
68. He, C., Klionsky, D.J., Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet., 43, 2009, 67.
69. Herman-Antosiewicz, A., Johnson, D.E., Singh, S.V., Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells. Cancer Res. 66:11 (2006), 5828–5835.
70. Hetz, C., Thielen, P., Matus, S., Nassif, M., Kiffin, R., Martinez, G., Cuervo, A.M., Brown, R.H., Glimcher, L.H., XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Gene. Dev. 23:19 (2009), 2294–2306.
71. Hou, Q., Tang, X., Liu, H., Tang, J., Yang, Y., Jing, X., Xiao, Q., Wang, W., Gou, X., Wang, Z., Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147. Cancer Sci. 102:7 (2011), 1287–1292.
72. Hou, W.-C., Lin, R.-D., Chen, C.-T., Lee, M.-H., Monoamine oxidase B (MAO-B) inhibition by active principles from Uncaria rhynchophylla. J. Ethnopharmacol. 100:1 (2005), 216–220.
73. Hsieh, M.-J., Tsai, T.-L., Hsieh, Y.-S., Wang, C.-J., Chiou, H.-L., Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines. Arch. Toxicol. 87:11 (2013), 1927–1937.
74. Huang, H.-C., Syu, K.-Y., Lin, J.-K., Chemical composition of Solanum nigrum linn extract and induction of autophagy by leaf water extract and its major flavonoids in AU565 breast cancer cells. J. Agric. Food Chem. 58:15 (2010), 8699–8708.
75. Inoki, K., Zhu, T., Guan, K.-L., TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:5 (2003), 577–590.
76. Itakura, E., Kishi, C., Inoue, K., Mizushima, N., Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell 19:12 (2008), 5360–5372.
77. Jaramillo, M.C., Zhang, D.D., The emerging role of the Nrf2–Keap1 signaling pathway in cancer. Gene. Dev. 27:20 (2013), 2179–2191.
78. Jefferies, H.B., Fumagalli, S., Dennis, P.B., Reinhard, C., Pearson, R.B., Thomas, G., Rapamycin suppresses 5' TOP mRNA translation through inhibition of p70s6k. EMBO J. 16:12 (1997), 3693–3704.
79. Jellinger, K.A., Basic mechanisms of neurodegeneration: a critical update. J. Cell Mol. Med 14:3 (2010), 457–487.
80. Jeong, K.H., Jung, U.J., Kim, S.R., Naringin attenuates autophagic stress and neuroinflammation in kainic acid-treated hippocampus in vivo. Evid.-Based Comp. Alt., 2015, 2015.
81. Jiang, H., Sun, J., Xu, Q., Liu, Y., Wei, J., Young, C.Y., Yuan, H., Lou, H., Marchantin M: a novel inhibitor of proteasome induces autophagic cell death in prostate cancer cells. Cell Death Dis., 4(8), 2013, e761.
82. Jiang, K., Wang, W., Jin, X., Wang, Z., Ji, Z., Meng, G., Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells. Oncol. Rep. 33:6 (2015), 2711–2718.
83. Jiang, T.-F., Zhang, Y.-J., Zhou, H.-Y., Wang, H.-M., Tian, L.-P., Liu, J., Ding, J.-Q., Chen, S.-D., Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of parkinson's disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy. J. Neuroimmune Pharm. 8:1 (2013), 356–369.
84. Jiang, W., Wei, W., Gaertig, M.A., Li, S., Li, X.-J., Therapeutic effect of berberine on Huntington's disease transgenic mouse model. PloS One, 10(7), 2015, e0134142.
85. Joshi, V.C., Avula, B., Khan, I.A., Authentication of Stephania tetrandra S. Moore (Fang Ji) and differentiation of its common adulterants using microscopy and HPLC analysis. J. Nat. Med. 62:1 (2008), 117–121.
86. Jung, C.H., Jun, C.B., Ro, S.-H., Kim, Y.-M., Otto, N.M., Cao, J., Kundu, M., Kim, D.-H., ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol. Biol. Cell 20:7 (2009), 1992–2003.
87. Kahle, P.J., Waak, J., Gasser, T., DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders. Free Radic. Biol. Med. 47:10 (2009), 1354–1361.
88. Kang, M., Jung, I., Hur, J., Kim, S.H., Lee, J.H., Kang, J.-Y., Jung, K.C., Kim, K.S., Yoo, M.C., Park, D.-S., The analgesic and anti-inflammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo. J. Ethnopharmacol. 131:2 (2010), 485–496.
89. Karakaş, H.E., GÖZÜAÇIK, D., Autophagy and cancer. Turk. J. Biol. 38:6 (2014), 720–739.
90. Kesidou, E., Lagoudaki, R., Touloumi, O., Poulatsidou, K.-N., Simeonidou, C., Autophagy and neurodegenerative disorders. Neural Regen. Res., 8(24), 2013, 2275.
91. Kim, H.-J., Lee, H.J., Jeong, S.-J., Lee, H.-J., Kim, S.-H., Park, E.-J., Cortex Mori Radicis extract exerts antiasthmatic effects via enhancement of CD4+ CD25+ Foxp3+ regulatory T cells and inhibition of Th2 cytokines in a mouse asthma model. J. Ethnopharmacol. 138:1 (2011), 40–46.
92. KIM, H.J., SEO, D.I., KIM, Y.M., 2013. Ethanol extract of Cinnamomum camphora suppresses proliferation and migration of HT1080 fibrosarcoma cells through the Akt/mTOR/VASP signaling patheway. 한국생물공학회학술대회. pp. 295–295.
93. Kirisako, T., Baba, M., Ishihara, N., Miyazawa, K., Ohsumi, M., Yoshimori, T., Noda, T., Ohsumi, Y., Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J. Cell Biol. 147:2 (1999), 435–446.
94. Knuesel, O., Weber, M., Suter, A., Arnica montana gel in osteoarthritis of the knee: an open, multicenter clinical trial. Adv. Ther. 19:5 (2002), 209–218.
95. Komatsu, M., Waguri, S., Koike, M., Sou, Y.-s., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-i., Ezaki, J., Murata, S., Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131:6 (2007), 1149–1163.
96. Komatsu, M., Kurokawa, H., Waguri, S., Taguchi, K., Kobayashi, A., Ichimura, Y., Sou, Y.-S., Ueno, I., Sakamoto, A., Tong, K.I., The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat. Cell Biol. 12:3 (2010), 213–223.
97. Kou, J., Sun, Y., Lin, Y., Cheng, Z., Zheng, W., Yu, B., Xu, Q., Anti-inflammatory activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents. Biol. Pharm. Bull. 28:7 (2005), 1234–1238.
98. Krosch, T.C., Sangwan, V., Banerjee, S., Mujumdar, N., Dudeja, V., Saluja, A.K., Vickers, S.M., Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor–kappa B activity. Am. J. Surg. 205:4 (2013), 387–396.
99. Ku, Y.-R., Wen, K.-C., Ho, L.-K., Chang, Y.-S., Solid-phase extraction for the determination of caffeine in traditional Chinese medicinal prescriptions containing Theae folium by high performance liquid chromatography. J. Pharm. Biomed. Anal. 20:1 (1999), 351–356.
100. Kuballa, P., Huett, A., Rioux, J.D., Daly, M.J., Xavier, R.J., Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PloS One, 3(10), 2008, e3391.
101. Kuo, P.-L., Hsu, Y.-L., Cho, C.-Y., Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol. Cancer Ther. 5:12 (2006), 3209–3221.
102. Kuo, Y.-F., Su, Y.-Z., Tseng, Y.-H., Wang, S.-Y., Wang, H.-M., Chueh, P.J., Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells. Free Radic. Biol. Med. 49:2 (2010), 214–226.
103. Lao, Y., Wan, G., Liu, Z., Wang, X., Ruan, P., Xu, W., Xu, D., Xie, W., Zhang, Y., Xu, H., The natural compound oblongifolin C inhibits autophagic flux and enhances antitumor efficacy of nutrient deprivation. Autophagy 10:5 (2014), 736–749.
104. Law, B.Y.K., Chan, W.K., Xu, S.W., Wang, J.R., Bai, L.P., Liu, L., Wong, V.K.W., Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells. Sci. Rep., 2014, 4.
105. Lee, J.-H., Yu, W.H., Kumar, A., Lee, S., Mohan, P.S., Peterhoff, C.M., Wolfe, D.M., Martinez-Vicente, M., Massey, A.C., Sovak, G., Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:7 (2010), 1146–1158.
106. Levine, B., Klionsky, D.J., Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6:4 (2004), 463–477.
107. Levine, B., Kroemer, G., Autophagy in the pathogenesis of disease. Cell 132:1 (2008), 27–42.
108. Levine, B., Mizushima, N., Virgin, H.W., Autophagy in immunity and inflammation. Nature 469:7330 (2011), 323–335.
109. Li, A., Zhu, Y., He, X., Tian, X., Xu, L., Ni, W., Jiang, P., Evaluation of antimicrobial activity of certain Chinese plants used in folkloric medicine. World J. Microbiol. Biotechnol. 24:4 (2008), 569–572.
110. Li, G., Rivas, P., Bedolla, R., Thapa, D., Reddick, R.L., Ghosh, R., Kumar, A.P., Dietary resveratrol prevents development of high-grade prostatic intraepithelial neoplastic lesions: involvement of SIRT1/S6K axis. Cancer Prev. Res. 6:1 (2013), 27–39.
111. Li, H.-b., Yi, X., Gao, J.-m., Ying, X.-x., Guan, H.-q., Li, J.-c., Magnolol-lnduced H460 cells deathvia autophagy but not apoptosis. Arch. Pharmacal Res. 30:12 (2007), 1566–1574.
112. Li, T., Xu, G., Wu, L., Sun, C., Pharmacological studies on the sedative and hypnotic effect of salidroside from the Chinese medicinal plant Rhodiola sachalinensis. Phytomedicine 14:9 (2007), 601–604.
113. Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B.-H., Jung, J.U., Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat. Cell Biol. 8:7 (2006), 688–698.
114. Liang, X.H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., Levine, B., Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:6762 (1999), 672–676.
115. Liao, X., Sluimer, J.C., Wang, Y., Subramanian, M., Brown, K., Pattison, J.S., Robbins, J., Martinez, J., Tabas, I., Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab. 15:4 (2012), 545–553.
116. Lim, C.B., Fu, P.Y., Ky, N., Zhu, H.S., Feng, X., Li, J., Srinivasan, K.G., Hamza, M.S., Zhao, Y., NF-κB p65 repression by the sesquiterpene lactone, Helenalin, contributes to the induction of autophagy cell death. BMC Complem. Altern. M, 12(1), 2012, 93.
117. Lin, C., Tsai, S.-C., Tseng, M.T., Peng, S.-F., Kuo, S.-C., Lin, M.-W., Hsu, Y.-M., Lee, M.-R., Amagaya, S., Huang, W.-W., AKT serine/threonine protein kinase modulates baicalin-triggered autophagy in human bladder cancer T24 cells. Int. J. Oncol. 42:3 (2013), 993–1000.
118. Lin, H.-M., Tseng, H.-C., Wang, C.-J., Chyau, C.-C., Liao, K.-K., Peng, P.-L., Chou, F.-P., Induction of autophagy and apoptosis by the extract of Solanum nigrum Linn in HepG2 cells. J. Agric. Food Chem. 55:9 (2007), 3620–3628.
119. Lin, H.-M., Tseng, H.-C., Wang, C.-J., Lin, J.-J., Lo, C.-W., Chou, F.-P., Hepatoprotective effects of Solanum nigrum Linn extract against CCl 4-iduced oxidative damage in rats. Chem. Biol. Interact. 171:3 (2008), 283–293.
120. Liu, A.-J., Wang, S.-H., Chen, K.-C., Kuei, H.-P., Shih, Y.-L., Hou, S.-Y., Chiu, W.-T., Hsiao, S.-H., Shih, C.-M., Evodiamine, a plant alkaloid, induces calcium/JNK-mediated autophagy and calcium/mitochondria-mediated apoptosis in human glioblastoma cells. Chem. Biol. Interact. 205:1 (2013), 20–28.
121. Liu, A.-J., Wang, S.-H., Hou, S.-Y., Lin, C.-J., Chiu, W.-T., Hsiao, S.-H., Chen, T.-H., Shih, C.-M., Evodiamine induces transient receptor potential vanilloid-1-mediated protective autophagy in U87-MG astrocytes. Evid. Based Compl. Alt., 2013, 2013.
122. Liu, Z., Li, X., Simoneau, A.R., Jafari, M., Zi, X., Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy. Mol. Carcinog. 51:3 (2012), 257–267.
123. Li-Weber, M., New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer. Rev. 35:1 (2009), 57–68.
124. Lock, R., Roy, S., Kenific, C.M., Su, J.S., Salas, E., Ronen, S.M., Debnath, J., Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol. Biol. Cell 22:2 (2011), 165–178.
125. Lock, R., Kenific, C.M., Leidal, A.M., Salas, E., Debnath, J., Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Disco. 4:4 (2014), 466–479.
126. Lu, J., Sun, D., Gao, S., Gao, Y., Ye, J., Liu, P., Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cells. J. Pharmacol. Sci. 125:1 (2014), 74–82.
127. Lu, J.-H., Tan, J.-Q., Durairajan, S.S.K., Liu, L.-F., Zhang, Z.-H., Ma, L., Shen, H.-M., Chan, H.E., Li, M., Isorhynchophylline, a natural alkaloid, promotes the degradation of alpha-synuclein in neuronal cells via inducing autophagy. Autophagy 8:1 (2012), 98–108.
128. Lu, L., Qin, A., Huang, H., Zhou, P., Zhang, C., Liu, N., Li, S., Wen, G., Zhang, C., Dong, W., Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition. Eur. J. Pharmacol. 658:2 (2011), 242–247.
129. Lu, Y., Ma, W., Hu, R., Dai, X., Pan, Y., Ionic liquid-based microwave-assisted extraction of phenolic alkaloids from the medicinal plant Nelumbo nucifera Gaertn. J. Chromatogr. A 1208:1 (2008), 42–46.
130. Lu, Z., Luo, R.Z., Lu, Y., Zhang, X., Yu, Q., Khare, S., Kondo, S., Kondo, Y., Yu, Y., Mills, G.B., The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J. Clin. Invest., 118(12), 2008, 3917.
131. Ma, Y., Galluzzi, L., Zitvogel, L., Kroemer, G., Autophagy and cellular immune responses. Immunity 39:2 (2013), 211–227.
132. Mai, T.T., Moon, J., Song, Y., Viet, P.Q., Van Phuc, P., Lee, J.M., Yi, T.-H., Cho, M., Cho, S.K., Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells. Cancer Lett. 321:2 (2012), 144–153.
133. Maiuri, M., Tasdemir, E., Criollo, A., Morselli, E., Vicencio, J., Carnuccio, R., Kroemer, G., Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ. 16:1 (2009), 87–93.
134. Maiuri, M.C., Le Toumelin, G., Criollo, A., Rain, J.C., Gautier, F., Juin, P., Tasdemir, E., Pierron, G., Troulinaki, K., Tavernarakis, N., Functional and physical interaction between Bcl‐XL and a BH3‐like domain in Beclin‐1. EMBO J. 26:10 (2007), 2527–2539.
135. Martinet, W., Agostinis, P., Vanhoecke, B., Dewaele, M., de Meyer, G., Autophagy in disease: a double-edged sword with therapeutic potential. Clin. Sci. 116 (2009), 697–712.
136. Martinez-Vicente, M., Talloczy, Z., Wong, E., Tang, G., Koga, H., Kaushik, S., de Vries, R., Arias, E., Harris, S., Sulzer, D., Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nat. Neurosci. 13:5 (2010), 567–576.
137. Martinez-Vicente, M., 2015. Autophagy in neurodegenerative diseases: From pathogenic dysfunction to therapeutic modulation, Semin. Cell Dev. Biol. Elsevier, pp. 115–126.
138. Mathew, R., Kongara, S., Beaudoin, B., Karp, C.M., Bray, K., Degenhardt, K., Chen, G., Jin, S., White, E., Autophagy suppresses tumor progression by limiting chromosomal instability. Gene. Dev. 21:11 (2007), 1367–1381.
139. Mathew, R., Karantza‐Wadsworth, V., White, E., Assessing metabolic stress and autophagy status in epithelial tumors. Methods Enzym. 453 (2009), 53–81.
140. Mathew, R., Karp, C.M., Beaudoin, B., Vuong, N., Chen, G., Chen, H.-Y., Bray, K., Reddy, A., Bhanot, G., Gelinas, C., Autophagy suppresses tumorigenesis through elimination of p62. Cell 137:6 (2009), 1062–1075.
141. Mei, Y., Thompson, M.D., Cohen, R.A., Tong, X., Autophagy and oxidative stress in cardiovascular diseases. BBA-Mol. Basis Dis. 1852:2 (2015), 243–251.
142. Meschini, S., Condello, M., Marra, M., Formisano, G., Federici, E., Arancia, G., Autophagy-mediated chemosensitizing effect of the plant alkaloid voacamine on multidrug resistant cells. Toxicol. In. Vitr. 21:2 (2007), 197–203.
143. Meschini, S., Condello, M., Calcabrini, A., Marra, M., Formisano, G., Lista, P., De Milito, A., Federici, E., Arancia, G., The plant alkaloid voacamine induces apoptosis-independent autophagic cell death on both sensitive and multidrug resistant human osteosarcoma cells. Autophagy 4:8 (2008), 1020–1033.
144. Michiorri, S., Gelmetti, V., Giarda, E., Lombardi, F., Romano, F., Marongiu, R., Nerini-Molteni, S., Sale, P., Vago, R., Arena, G., The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy. Cell Death Differ. 17:6 (2010), 962–974.
145. Millecamps, S., Julien, J.-P., Axonal transport deficits and neurodegenerative diseases. Nat. Rev. Neurosci. 14:3 (2013), 161–176.
146. Mizushima, N., Autophagy: process and function. Gene. Dev. 21:22 (2007), 2861–2873.
147. Mizushima, N., The role of the Atg1/ULK1 complex in autophagy regulation. Curr. Opin. Cell Biol. 22:2 (2010), 132–139.
148. Mizushima, N., Komatsu, M., Autophagy: renovation of cells and tissues. Cell 147:4 (2011), 728–741.
149. Mizushima, N., Noda, T., Ohsumi, Y., Apg16p is required for the function of the Apg12p–Apg5p conjugate in the yeast autophagy pathway. EMBO J. 18:14 (1999), 3888–3896.
150. Mizushima, N., Levine, B., Cuervo, A.M., Klionsky, D.J., Autophagy fights disease through cellular self-digestion. Nature 451:7182 (2008), 1069–1075.
151. Moscat, J., Diaz-Meco, M.T., P62 at the crossroads of autophagy. apoptosis, Cancer Cell 137:6 (2009), 1001–1004.
152. Moscat, J., Diaz-Meco, M.T., P62: a versatile multitasker takes on cancer. Trends Biochem. Sci. 37:6 (2012), 230–236.
153. Münz, C., Enhancing immunity through autophagy. Annu. Rev. Immunol. 27 (2009), 423–449.
154. Nishino, I., Fu, J., Tanji, K., Yamada, T., Shimojo, S., Koori, T., Mora, M., Riggs, J.E., Oh, S.J., Koga, Y., Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406:6798 (2000), 906–910.
155. Nixon, R.A., Autophagy, amyloidogenesis and Alzheimer disease. J. Cell Sci. 120:23 (2007), 4081–4091.
156. Nixon, R.A., The role of autophagy in neurodegenerative disease. Nat. Med. 19:8 (2013), 983–997.
157. Nixon, R.A., Wegiel, J., Kumar, A., Yu, W.H., Peterhoff, C., Cataldo, A., Cuervo, A.M., Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J. Neuropath. Exp. Neur. 64:2 (2005), 113–122.
158. Obara, K., Sekito, T., Niimi, K., Ohsumi, Y., The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J. Biol. Chem. 283:35 (2008), 23972–23980.
159. Oh, S.H., Kim, Y.S., Lim, S.C., Hou, Y.F., Chang, I.Y., You, H.J., Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner. Autophagy 4:8 (2008), 1009–1019.
160. Opipari, A.W., Tan, L., Boitano, A.E., Sorenson, D.R., Aurora, A., Liu, J.R., Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res. 64:2 (2004), 696–703.
161. Ouyang, D.-y., Zeng, L.-h., Pan, H., Xu, L.-h., Wang, Y., Liu, K.-p., He, X.-h., Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy. Food Chem. Toxicol. 60 (2013), 424–430.
162. Padhi, P., 2014. Terminalia bellerica (baheda) inhibits protective autophagy and induces apoptosis in oral cancer cell lines.
163. Parikh, A.A., Yang, X.-Y., Zeng, F.-D., Salama, G., Dauricine suppresses early afterdepolarizations and Torsade De Pointes in rabbit hearts with long Qt2 syndrome. Circulation, 124(21S), 2011, A8917.
164. Park, H.S., Kim, G.Y., Nam, T.J., Deuk Kim, N., Hyun Choi, Y., Antiproliferative activity of fucoi J. Food Sci. an was associated with the induction of apoptosis and autophagy in AGS human gastric cancer cells. J. Food Sci. 76:3 (2011), T77–T83.
165. Park, M., Cheon, M.S., Kim, S.H., Chun, J.M., Lee, A.Y., Moon, B.C., Yoon, T., Choo, B.K., Kim, H.K., Anticancer activity of Asparagus cochinchinensis extract and fractions in HepG2 cells. J. Korean Soc. Appl. Bl. 54:2 (2011), 188–193.
166. Park, S.-H., Chi, G.Y., Eom, H.S., Kim, G.-Y., Hyun, J.W., Kim, W.-J., Lee, S.-J., Yoo, Y.H., Choi, Y.H., Role of autophagy in apoptosis induction by methylene chloride extracts of Mori cortex in NCI-H460 human lung carcinoma cells. Int. J. Oncol. 40:6 (2012), 1929–1940.
167. Park, S.-H., Park, H.S., Lee, J.H., Chi, G.Y., Kim, G.-Y., Moon, S.-K., Chang, Y.-C., Hyun, J.W., Kim, W.-J., Choi, Y.H., Induction of endoplasmic reticulum stress-mediated apoptosis and non-canonical autophagy by luteolin in NCI-H460 lung carcinoma cells. Food Chem. Toxicol. 56 (2013), 100–109.
168. Parkes, M., Barrett, J.C., Prescott, N.J., Tremelling, M., Anderson, C.A., Fisher, S.A., Roberts, R.G., Nimmo, E.R., Cummings, F.R., Soars, D., Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Genet. 39:7 (2007), 830–832.
169. Parzych, K.R., Klionsky, D.J., An overview of autophagy: morphology, mechanism, and regulation. Antioxid. Redox Sign 20:3 (2014), 460–473.
170. Peng, P.-l., Kuo, W.-H., Tseng, H.-C., Chou, F.-P., Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death. Int. J. Radiat. Oncol. L 70:2 (2008), 529–542.
171. Pickford, F., Masliah, E., Britschgi, M., Lucin, K., Narasimhan, R., Jaeger, P.A., Small, S., Spencer, B., Rockenstein, E., Levine, B., The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J. Clin. Invest., 118(6), 2008, 2190.
172. Pierdominici, M., Vomero, M., Barbati, C., Colasanti, T., Maselli, A., Vacirca, D., Giovannetti, A., Malorni, W., Ortona, E., Role of autophagy in immunity and autoimmunity, with a special focus on systemic lupus erythematosus. FASEB J. 26:4 (2012), 1400–1412.
173. Poornima, P., Weng, C.F., Padma, V.V., Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells. Food Chem. 141:4 (2013), 3598–3605.
174. Psahoulia, F.H., Moumtzi, S., Roberts, M.L., Sasazuki, T., Shirasawa, S., Pintzas, A., Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha-RAS-transformed human colon cells. Carcinogenesis 28:5 (2007), 1021–1031.
175. Puissant, A., Robert, G., Fenouille, N., Luciano, F., Cassuto, J.-P., Raynaud, S., Auberger, P., Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res. 70:3 (2010), 1042–1052.
176. Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest., 112(12), 2003, 1809.
177. Rafatian, G., Khodagholi, F., Farimani, M.M., Abraki, S.B., Gardaneh, M., Increase of autophagy and attenuation of apoptosis by Salvigenin promote survival of SH-SY5Y cells following treatment with H2O2. Mol. Cell. Biochem. 371:1–2 (2012), 9–22.
178. Ravikumar, B., Rubinsztein, D.C., Can autophagy protect against neurodegeneration caused by aggregate-prone proteins?. Neuroreport 15:16 (2004), 2443–2445.
179. Ravikumar, B., Vacher, C., Berger, Z., Davies, J.E., Luo, S., Oroz, L.G., Scaravilli, F., Easton, D.F., Duden, R., O'Kane, C.J., Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36:6 (2004), 585–595.
180. Rodríguez-Navarro, J.A., Rodríguez, L., Casarejos, M.J., Solano, R.M., Gómez, A., Perucho, J., Cuervo, A.M., de Yébenes, J.G., Mena, M.A., Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation. Neuro. Biol. Dis. 39:3 (2010), 423–438.
181. Saiki, S., Sasazawa, Y., Imamichi, Y., Kawajiri, S., Fujimaki, T., Tanida, I., Kobayashi, H., Sato, F., Sato, S., Ishikawa, K.-I., Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy 7:2 (2011), 176–187.
182. Sarkar, S., Davies, J.E., Huang, Z., Tunnacliffe, A., Rubinsztein, D.C., Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and α-synuclein. J. Biol. Chem. 282:8 (2007), 5641–5652.
183. Sarkar, S., Perlstein, E.O., Imarisio, S., Pineau, S., Cordenier, A., Maglathlin, R.L., Webster, J.A., Lewis, T.A., O'Kane, C.J., Schreiber, S.L., Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat. Chem. Biol. 3:6 (2007), 331–338.
184. Sarkar, S., Ravikumar, B., Floto, R., Rubinsztein, D., Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 16:1 (2009), 46–56.
185. Sasazawa, Y., Sato, N., Umezawa, K., Simizu, S., Conophylline protects cells in cellular models of neurodegenerative diseases by inducing mammalian target of rapamycin (mTOR)-independent autophagy. J. Biol. Chem. 290:10 (2015), 6168–6178.
186. Scarlatti, F., Maffei, R., Beau, I., Codogno, P., Ghidoni, R., Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell Death Differ. 15:8 (2008), 1318–1329.
187. Schaeffer, V., Lavenir, I., Ozcelik, S., Tolnay, M., Winkler, D.T., Goedert, M., Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy. Brain 135:7 (2012), 2169–2177.
188. Schmeisser, H., Bekisz, J., Zoon, K.C., New function of type I IFN: induction of autophagy. J. Interf. Cytok. Res. 34:2 (2014), 71–78.
189. Schwikkard, S., van Heerden, F.R., Antimalarial activity of plant metabolites. Nat. Prod. Rep. 19:6 (2002), 675–692.
190. Shi, S., Cao, H., Shikonin promotes autophagy in BXPC‑3 human pancreatic cancer cells through the PI3K/Akt signaling pathway. Oncol. Lett. 8:3 (2014), 1087–1089.
191. Shintani, T., Klionsky, D.J., Autophagy in health and disease: a double-edged sword. Science 306:5698 (2004), 990–995.
192. Son, J.H., Shim, J.H., Kim, K.-H., Ha, J.-Y., Han, J.Y., Neuronal autophagy and neurodegenerative diseases. Exp. Mol. Med. 44:2 (2012), 89–98.
193. Spencer, B., Potkar, R., Trejo, M., Rockenstein, E., Patrick, C., Gindi, R., Adame, A., Wyss-Coray, T., Masliah, E., Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in α-synuclein models of Parkinson's and Lewy body diseases. J. Neurosci. 29:43 (2009), 13578–13588.
194. Steelman, L.S., Chappell, W.H., Abrams, S.L., Kempf, C.R., Long, J., Laidler, P., Mijatovic, S., Maksimovic-Ivanic, D., Stivala, F., Mazzarino, M.C., Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging, 3(3), 2011, 192.
195. Strømhaug, P.E., Reggiori, F., Guan, J., Wang, C.-W., Klionsky, D.J., Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy. Mol. Biol. Cell 15:8 (2004), 3553–3566.
196. Suh, Y., Afaq, F., Khan, N., Johnson, J.J., Khusro, F.H., Mukhtar, H., Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells. Carcinogenesis 31:8 (2010), 1424–1433.
197. Sy, L.-K., Yan, S.-C., Lok, C.-N., Man, R.Y., Che, C.-M., Timosaponin A-III induces autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells. Cancer Res 68:24 (2008), 10229–10237.
198. Tamayo, C., Diamond, S., Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.). Integr. Cancer Ther. 6:2 (2007), 146–157.
199. Tang, D., Kang, R., Livesey, K.M., Cheh, C.-W., Farkas, A., Loughran, P., Hoppe, G., Bianchi, M.E., Tracey, K.J., Zeh, H.J., Endogenous HMGB1 regulates autophagy. J. Cell Biol. 190:5 (2010), 881–892.
200. Tannous, P., Zhu, H., Johnstone, J.L., Shelton, J.M., Rajasekaran, N.S., Benjamin, I.J., Nguyen, L., Gerard, R.D., Levine, B., Rothermel, B.A., Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc. Natl. Acad. Sci. 105:28 (2008), 9745–9750.
201. Tasdemir, E., Maiuri, M.C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., Regulation of autophagy by cytoplasmic p53. Nat. Cell Biol. 10:6 (2008), 676–687.
202. Tasdemir, E., Maiuri, M.C., Orhon, I., Kepp, O., Morselli, E., Criollo, A., Kroemer, G., P53 represses autophagy in a cell cycle-dependent fashion. Cell Cycle 7:19 (2008), 3006–3011.
203. Teffo, L.S., Aderogba, M., Eloff, J.N., Antibacterial and antioxidant activities of four kaempferol methyl ethers isolated from Dodonaea viscosa Jacq. var. angustifolia leaf extracts. South Afr. J. Bot. 76:1 (2010), 25–29.
204. TELLEZ-NAGEL, I., JOHNSON, A.B., TERRY, R.D., Studies on brain biopsies of patients with Huntington's chorea. J. Neuropathol. Exp. Neurol. 33:2 (1974), 308–332.
205. Vingtdeux, V., Giliberto, L., Zhao, H., Chandakkar, P., Wu, Q., Simon, J.E., Janle, E.M., Lobo, J., Ferruzzi, M.G., Davies, P., AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-β peptide metabolism. J. Biol. Chem. 285:12 (2010), 9100–9113.
206. Viry, E., Paggetti, J., Baginska, J., Mgrditchian, T., Berchem, G., Moussay, E., Janji, B., Autophagy: an adaptive metabolic response to stress shaping the antitumor immunity. Biochem. Pharmacol. 92:1 (2014), 31–42.
207. Vogiatzi, T., Xilouri, M., Vekrellis, K., Stefanis, L., Wild type α-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J. Biol. Chem. 283:35 (2008), 23542–23556.
208. Wang, H., Liu, J., Gao, G., Wu, X., Wang, X., Yang, H., Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury. Brain Res., 2015.
209. Wang, K., Liu, R., Li, J., Mao, J., Lei, Y., Wu, J., Zeng, J., Zhang, T., Wu, H., Chen, L., Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR-and hypoxia-induced factor 1α-mediated signaling. Autophagy 7:9 (2011), 966–978.
210. Wang, N., Feng, Y., Zhu, M., Tsang, C.M., Man, K., Tong, Y., Tsao, S.W., Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism. J. Cell. Biochem. 111:6 (2010), 1426–1436.
211. Wang, N., Pan, W., Zhu, M., Zhang, M., Hao, X., Liang, G., Feng, Y., Fangchinoline induces autophagic cell death via p53/sestrin2/AMPK signalling in human hepatocellular carcinoma cells. Br. J. Pharm. 164:2b (2011), 731–742.
212. Weckman, A., Rotondo, F., Di Ieva, A., Syro, L.V., Butz, H., Cusimano, M., Kovacs, K., Autophagy in endocrine tumors. Endocr. Relat. Cancer ERC-, 2015, 15–0042.
213. Wen, Y.-D., Sheng, R., Zhang, L.-S., Han, R., Zhang, X., Zhang, X.-D., Han, F., Fukunaga, K., Qin, Z.-H., Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy 4:6 (2008), 762–769.
214. White, E., Deconvoluting the context-dependent role for autophagy in cancer. Nat. Rev. Cancer 12:6 (2012), 401–410.
215. White, E., The role for autophagy in cancer. J. Clin. Invest. 125:1 (2015), 42–46.
216. Winslow, A.R., Chen, C.-W., Corrochano, S., Acevedo-Arozena, A., Gordon, D.E., Peden, A.A., Lichtenberg, M., Menzies, F.M., Ravikumar, B., Imarisio, S., α-Synuclein impairs macroautophagy: implications for Parkinson's disease. J. Cell Biol. 190:6 (2010), 1023–1037.
217. Wong, V.K., Li, T., Law, B.Y., Ma, E.D., Yip, N., Michelangeli, F., Law, C.K., Zhang, M., Lam, K.Y., Chan, P., Saikosaponin-d, a novel SERC. J. Cell Biol., 2013, 720.
218. Wong, V.K.W., Wu, A.G., Wang, J.R., Liu, L., Law, B.Y.-K., Neferine attenuates the protein level and toxicity of mutant huntingtin in PC-12 cells via induction of autophagy. Molecule 20:3 (2015), 3496–3514.
219. Wu, A.-G., Wong, V.K.-W., Xu, S.-W., Chan, W.-K., Ng, C.-I., Liu, L., Law, B.Y.-K., Onjisaponin B derived from Radix Polygalae enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin in PC-12 cells. Int. J. Mol. Sci. 14:11 (2013), 22618–22641.
220. Wu, Y., Li, X., Zhu, J.X., Xie, W., Le, W., Fan, Z., Jankovic, J., Pan, T., Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease. Neurosignals 19:3 (2011), 163–174.
221. Xia, Y.-h., Cheng, C.-r., Yao, S.-y., Zhang, Q., Wang, Y., Ji, Z.-n., L-Securinine induced the human colon cancer SW480 cell autophagy and its molecular mechanism. Fitoterapia 82:8 (2011), 1258–1264.
222. Xiang, Y.Z., Shang, H.C., Gao, X.M., Zhang, B.L., A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytother. Res. 22:7 (2008), 851–858.
223. Xie, Y., Fan, M., Jiang, R., Wang, Z., Li, Y., Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma FaDu cell. Neoplasma 62:3 (2014), 419–431.
224. Xu, J., Wang, H., Lu, X., Ding, K., Zhang, L., He, J., Wei, W., Wu, Y., Posttraumatic administration of luteolin protects mice from traumatic brain injury: implication of autophagy and inflammation. Brain Res. 1582 (2014), 237–246.
225. Xu, M.-Y., Lee, D.H., Joo, E.J., Son, K.H., Kim, Y.S., Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells. Food Chem. Toxicol. 59 (2013), 703–708.
226. Xu, M.-Y., Lee, S.Y., Kang, S.S., Kim, Y.S., Antitumor activity of jujuboside B and the underlying mechanism via induction of apoptosis and autophagy. J. Nat. Prod. 77:2 (2014), 370–376.
227. Xu, Y., Tian, C., Sun, J., Zhang, J., Ren, K., Fan, X.-Y., Wang, K., Wang, H., Yan, Y.-E., Chen, C., FBXW7-induced MTOR degradation forces autophagy to counteract persistent prion infection. Mol. Neurobiol. 53:1 (2016), 706–719.
228. Yang, H.-L., Chen, S.-C., Chen, C.-S., Wang, S.-Y., Hseu, Y.-C., Alpinia pricei rhizome extracts induce apoptosis of human carcinoma KB cells via a mitochondria-dependent apoptotic pathway. Food Chem. Toxicol. 46:10 (2008), 3318–3324.
229. Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J.M., Dell'Antonio, G., Pancreatic cancers require autophagy for tumor growth. Gene. Dev. 25:7 (2011), 717–729.
230. Yang, Z.J., Chee, C.E., Huang, S., Sinicrope, F.A., The role of autophagy in cancer: therapeutic implications. Mol. Cancer Ther. 10:9 (2011), 1533–1541.
231. Young, A.R., Narita, M., Ferreira, M., Kirschner, K., Sadaie, M., Darot, J.F., Tavaré, S., Arakawa, S., Shimizu, S., Watt, F.M., Autophagy mediates the mitotic senescence transition. Gene. Dev. 23:7 (2009), 798–803.
232. Yu, W.H., Cuervo, A.M., Kumar, A., Peterhoff, C.M., Schmidt, S.D., Lee, J.-H., Mohan, P.S., Mercken, M., Farmery, M.R., Tjernberg, L.O., Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease. J. Cell Biol. 171:1 (2005), 87–98.
233. Yue, Z., Jin, S., Yang, C., Levine, A.J., Heintz, N., Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. 100:25 (2003), 15077–15082.
234. Zalckvar, E., Berissi, H., Mizrachy, L., Idelchuk, Y., Koren, I., Eisenstein, M., Sabanay, H., Pinkas‐Kramarski, R., Kimchi, A., DAP‐kinase‐mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl‐XL and induction of autophagy. EMBO Rep. 10:3 (2009), 285–292.
235. Zaveri, M., Khandhar, A., Patel, S., Patel, A., Chemistry and pharmacology of Piper longum L. Int. J. Pharm. Sci. Rev. Res. 5:1 (2010), 67–76.
236. Zhang, J.-Q., Li, Y.-M., Liu, T., He, W.-T., Chen, Y.-T., Chen, X.-H., Li, X., Zhou, W.-C., Yi, J.-F., Ren, Z.-J., Antitumor effect of matrine in human hepatoma G2 cells by inducing apoptosis and autophagy. World J. Gastroenterol. 16:34 (2010), 4281–4290.
237. Zhang, T., Li, Y., Park, K.A., Byun, H.S., Won, M., Jeon, J., Lee, Y., Seok, J.H., Choi, S.-W., Lee, S.-H., Cucurbitacin induces autophagy through mitochondrial ROS production which counteracts to limit caspase-dependent apoptosis. Autophagy 8:4 (2012), 559–576.
238. Zheng, X., Xie, Z., Zhu, Z., Liu, Z., Wang, Y., Wei, L., Yang, H., Yang, H., Liu, Y., Bi, J., Methyllycaconitine alleviates amyloid-β peptides-induced cytotoxicity in SH-SY5Y cells. PloS One, 2014.
239. Zhou, J., Hu, S.-E., Tan, S.-H., Cao, R., Chen, Y., Xia, D., Zhu, X., Yang, X.-F., Ong, C.-N., Shen, H.-M., Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells. Autophagy 8:3 (2012), 338–349.
240. Zhou, J., Li, G., Zheng, Y., Shen, H.-M., Hu, X., Ming, Q.-L., Huang, C., Li, P., Gao, N., A novel autophagy/mitophagy inhibitor liensinine sensitizes breast cancer cells to chemotherapy through DNM1L-mediated mitochondrial fission. Autophagy 11:8 (2015), 1259–1279.
241. Zhu, H., Tannous, P., Johnstone, J.L., Kong, Y., Shelton, J.M., Richardson, J.A., Le, V., Levine, B., Rothermel, B.A., Hill, J.A., Cardiac autophagy is a maladaptive response to hemodynamic stress. J. Clin. Invest 117:7 (2007), 1782–1793.
242. Zhu, Y., Wang, J., Wogonin increases β-amyloid clearance and inhibits tau phosphorylation via inhibition of mammalian target of rapamycin: potential drug to treat Alzheimer's disease. Neurol. Sci., 2015, 1–8.
243. Zimmer, A.R., Leonardi, B., Miron, D., Schapoval, E., de Oliveira, J.R., Gosmann, G., Antioxidant and anti-inflammatory properties of Capsicum baccatum: from traditional use to scientific approach. J. Ethnopharmacol. 139:1 (2012), 228–233.