Autophagy inhibition in combination cancer treatment

Current Opinion in Investigational Drugs

Volumn 10, Issue 12, 2009, Pages 1269-1279

  Livesey, Kristen M ^a   Tang, Daolin ^a   Zeh, Herbert J ^a   Lotze, Michael T ^a  

^a UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

Author keywords

Autophagy; Cancer; Chloroquine; Chlorpromazine; Ethyl pyruvate; Glycyrrhizin; High mobility group box 1; Inhibitor; Therapeutic

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 3 METHYLADENINE; ADENOSINE TRIPHOSPHATASE INHIBITOR; ANTHOCYANIN; BAFILOMYCIN A1; BECLIN 1; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BENZYLOXYCARBONYLVALYLALANYLASPARTYL FLUOROMETHYL KETONE; CHLOROQUINE; CLOMIPRAMINE; FENRETINIDE; FLUOROURACIL; GEMCITABINE; GLYCYRRHIZIC ACID; GROWTH FACTOR; HIGH MOBILITY GROUP B1 PROTEIN; HYDROXYCHLOROQUINE; IMATINIB; OXALIPLATIN; PHORBOL 13 ACETATE 12 MYRISTATE; PLATINUM DERIVATIVE; PYRUVIC ACID DERIVATIVE; PYRUVIC ACID ETHYL ESTER; QUERCETIN; RTA 203; SALIPHENYLHALAMIDE; SMALL INTERFERING RNA; TAMOXIFEN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT; WORTMANNIN;

ABDOMINAL PAIN; ADVANCED CANCER; ANGIOGENESIS; APOPTOSIS; AUTOPHAGY; B CELL LEUKEMIA; B CELL LYMPHOMA; BACTERIAL INFECTION; BONE MARROW CELL; BRAIN TUMOR; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM TUMOR; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; COLON CANCER; COLORECTAL CANCER; CYTOSOL; DENDRITIC CELL; DNA REPAIR; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGETING; DRUG TOLERABILITY; ENDOPLASMIC RETICULUM STRESS; GENOMICS; GLIOBLASTOMA; GLIOMA; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; KIDNEY CANCER; LEUKEMIA; LUNG CANCER; LUNG NON SMALL CELL CANCER; LUPUS ERYTHEMATOSUS; MALARIA; MELANOMA; MULTIPLE MYELOMA; NAUSEA; NONHUMAN; NUTRIENT; OXIDATIVE STRESS; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PHARYNX CANCER; PLASMACYTOMA; PROSTATE CANCER; REGULATORY T LYMPHOCYTE; RETINOPATHY; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SOLID TUMOR; STEM CELL; TREATMENT OUTCOME; UTERINE CERVIX CANCER; VIRUS INFECTION; VOMITING;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; AUTOPHAGY; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, NEOPLASM; HMGB1 PROTEIN; HUMANS; NEOPLASMS;

EID: 71249122207     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (105)

1. Di Pietro C, Ragusa M, Barbagallo D, Duro LR, Guglielmino MR, Majorana A, Angelica R, Scalia M, Statello L, Salito L, Tomasello L et al: The apoptotic machinery as a biological complex system: Analysis of its omics and evolution, identification of candidate genes for fourteen major types of cancer, and experimental validation in CML and neuroblastoma. BMC Medical Genomics (2009) 2(1):20.
2. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M et al: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature (2009) 460(7253):392-395.
3. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R: Caloric restriction delays disease onset and mortality in rhesus monkeys. Science (2009) 325(5937): 201-204.
4. Galluzzi L, Morselli E, Vicencio JM, Kepp O, Joza N, Tajeddine N, Kroemer G: Life, death and burial: Multifaceted impact of autophagy. Biochem Soc Trans (2008) 36(Pt 5):786-790.
5. Kroemer G, Tolkovsky AM, Zakeri Z: Élan vital, élan létal: One life but multiple deaths. Cell Death Differ (2008) 15(7):1089-1090.
6. Vicencio JM, Galluzzi L, Tajeddine N, Ortiz C, Criollo A, Tasdemir E, Morselli E, Ben Younes A, Maiuri MC, Lavandero S, Kroemer G: Senescence, apoptosis or autophagy? When a damaged cell must decide its path - A mini-review. Gerontology (2008) 54(2):92-99.
7. Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, Fitzgerald P, Guio-Carrion A, Waterhouse NJ, Li CW, Mari B et al: GAPDH and autophagy preserve survival after apoptotic cytochrome C release in the absence of caspase activation. Cell (2007) 129(5):983-997.
8. White E: Role of the metabolic stress responses of apoptosis and autophagy in tumor suppression. Ernst Schering Foundation Symposium Proceedings (2007) (4):23-34.
9. Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, White E: Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev (2007) 21(13):1621-1635.
10. Jin S, White E: Tumor suppression by autophagy through the management of metabolic stress. Autophagy (2008) 4(5): 563-566.
11. Fujii S, Mitsunaga S, Yamazaki M, Hasebe T, Ishii G, Kojima M, Kinoshita T, Ueno T, Esumi H, Ochiai A: Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Sci (2008) 99(9):1813-1819.
12. Geng J, Klionsky DJ: The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: Beyond the usual suspects' review series. EMBO Rep (2008) 9(9):859-864.
13. Zakeri Z, Melendez A, Lockshin RA: Detection of autophagy in cell death. Methods Enzymol (2008) 442:289-306.
14. Mizushima N: Methods for monitoring autophagy. Int J Biochem Cell Biol (2004) 36(12):2491-2502.
15. Bampton ET, Goemans CG, Niranjan D, Mizushima N, Tolkovsky AM: The dynamics of autophagy visualized in live cells: From autophagosome formation to fusion with endo/lysosomes. Autophagy (2005) 1(1):23-36.
16. Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM: In situ detection of starvation-induced autophagy. J Histochem Cytochem (2006) 54(1):85-96.
17. Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM: Detection of autophagy in tissue by standard immunohistochemistry: Possibilities and limitations. Autophagy (2006) 2(1):55-57.
18. Tanida I, Ueno T, Kominami E: LC3 and autophagy. Methods Mol Biol (2008) 445:77-88.
19. Tanida I, Minematsu-Ikeguchi N, Ueno T, Kominami E: Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy (2005) 1(2):84-91.
20. Shvets E, Fass E, Elazar Z: Utilizing flow cytometry to monitor autophagy in living mammalian cells. Autophagy (2008) 4(5): 621-628.
21. Zhang L, Yu J, Pan H, Hu P, Hao Y, Cai W, Zhu H, Yu AD, Xie X, Ma D, Yuan J: Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci USA (2007) 104(48):19023-19028.
22. Kang R, Tang D, Schapiro NE, Livesey KM, Farkas A, Loughran P, Bierhaus A, Lotze MT, Zeh HJ: The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ (2009):doi:10.1038/cdd.2009.149
23. Liang X, Romo-Vivar A, Schapiro NE, Loughran P, Thorne SH, Amoscato AA, Zeh HJ, Beer-Stolz D, Lotze MT, de Vera ME: Ethyl pyruvate administration inhibits hepatic tumor growth. J Leukoc Biol (2009) 86(3):599-607.
24. Cheng BQ, Jia CQ, Liu CT, Lu XF, Zhong N, Zhang ZL, Fan W, Li YQ: Serum high mobility group box chromosomal protein 1 is associated with clinicopathologic features in patients with hepatocellular carcinoma. Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2008) 40(6):446-452.
25. Yamada S, Yakabe K, Ishii J, Imaizumi H, Maruyama I: New high mobility group box 1 assay system. Clin Chim Acta (2006) 372 (1-2):173-178.
26. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, Cattoretti G et al: Promotion of tumorigenesis by heterozygous disruption of the Beclin 1 autophagy gene. J Clin Invest (2003) 112(12):1809-1820.
27. Yue Z, Jin S, Yang C, Levine AJ, Heintz N: Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA (2003) 100(25):15077-15082.
28. Turcotte S, Chan DA, Sutphin PD, Hay MP, Denny WA, Giaccia AJ: A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy. Cancer Cell (2008) 14(1):90-102.
29. Kondo Y, Kanzawa T, Sawaya R, Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer (2005) 5(9):726-734.
30. Ogier-Denis E, Houri JJ, Bauvy C, Codogno P: Guanine nucleotide exchange on heterotrimeric Gi3 protein controls autophagic sequestration in HT-29 cells. J Biol Chem (1996) 271(45):28593-28600.
31. Liang XH, Yu J, Brown K, Levine B: Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function. Cancer Research (2001) 61(8):3443-3449.
32. Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A: WIPI-1a (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene (2004) 23(58):9314-9325.
33. Susan PP, Dunn WA: Starvation-induced lysosomal degradation of aldolase B requires glutamine 111 in a signal sequence for chaperone-mediated transport. J Cell Physiol (2001) 187(1):48-58.
34. Ito H, Daido S, Kanzawa T, Kondo S, Kondo Y: Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int J Oncol (2005) 26(5):1401-1410.
35. Kondo Y, Kondo S: Autophagy and cancer therapy. Autophagy (2006) 2(2):85-90.
36. Mathew R, Karantza-Wadsworth V, White E: Role of autophagy in cancer. Nat Rev Cancer (2007) 7(12):961-967.
37. Mathew R, White E: Why sick cells produce tumors: The protective role of autophagy. Autophagy (2007) 3(5):502-505.
38. Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H et al: Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med (2007) 13(9):1050-1059.
39. Boya P, González-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Métivier D, Meley D, Souquere S, Yoshimori T, Pierron G et al: Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol (2005) 25(3):1025-1040.
40. Seglen PO, Gordon PB: 3-Methyladenine: Specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA (1982) 79(6):1889-1892.
41. Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ, Codogno P: Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem (2000) 275(2):992-998.
42. Blommaart EF, Krause U, Schellens JP, Vreeling-Sindelárová H, Meijer AJ: The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem (1997) 243(1-2):240-246.
43. Kim PK, Hailey DW, Mullen RT, Lippincott-Schwartz J: Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci USA (2008) 105(52):20567-20574.
44. Tiwari M, Bajpai VK, Sahasrabuddhe AA, Kumar A, Sinha RA, Behari S, Godbole MM: Inhibition of N-(4-hydroxyphenyl) retinamide-induced autophagy at a lower dose enhances cell death in malignant glioma cells. Carcinogenesis (2008) 29(3): 600-609.
45. Ge PF, Zhang JZ, Wang XF, Meng FK, Li WC, Luan YX, Ling F, Luo YN: Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells. Acta Pharmacol Sin (2009) 30(7):1046-1052.
46. Li J, Hou N, Faried A, Tsutsumi S, Takeuchi T, Kuwano H: Inhibition of autophagy by 3-MA enhances the effect of 5-FUinduced apoptosis in colon cancer cells. Ann Surg Oncol (2009) 16(3):761-771.
47. Longo L, Platini F, Scardino A, Alabiso O, Vasapollo G, Tessitore L: Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma. Mol Cancer Ther (2008) 7(8):2476-2485.
48. Vercammen D, Beyaert R, Denecker G, Goossens V, Van Loo G, Declercq W, Grooten J, Fiers W, Vandenabeele P: Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med (1998) 187(9):1477-1485.
49. White E: Autophagic cell death unraveled: Pharmacological inhibition of apoptosis and autophagy enables necrosis. Autophagy (2008) 4(4):399-401.
50. Wu YT, Tan HL, Huang Q, Kim YS, Pan N, Ong WY, Liu ZG, Ong CN, Shen HM: Autophagy plays a protective role during zVADinduced necrotic cell death. Autophagy (2008) 4(4):457-466.
51. Lotze MT, Zeh HJ, Rubartelli A, Sparvero LJ, Amoscato AA, Washburn NR, Devera ME, Liang X, Tör M, Billiar T: The grateful dead: Damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol Rev (2007) 220:60-81.
52. Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y: Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct (1998) 23(1):33-42.
53. Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D, Yahalom J: A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Research (2001) 61(2):439-444.
54. Shingu T, Fujiwara K, Bögler O, Akiyama Y, Moritake K, Shinojima N, Tamada Y, Yokoyama T, Kondo S: Stage-specific effect of inhibition of autophagy on chemotherapy-induced cytotoxicity. Autophagy (2009) 5(4):537-539.
55. Shingu T, Fujiwara K, Bögler O, Akiyama Y, Moritake K, Shinojima N, Tamada Y, Yokoyama T, Kondo S: Inhibition of autophagy at a late stage enhances imatinib-induced cytotoxicity in human malignant glioma cells. Int J Cancer (2009) 124(5):1060-1071.
56. Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S: Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ (2004) 11(4):448-457. (Pubitemid 38489422)
57. Rutman RJ, Steele WJ, Price CC: Experimental chemotherapy studies. I. Chemical and metabolic investigations of chloroquine mustard. Cancer Research (1961) 21:1124-1133.
58. Rutman RJ, Steele WJ, Price CC: Experimental chemotherapy studies. II. The reactions of chloroquine mustard (CQM) and nitrogen mustard (HN2) with Ehrlich cells. Cancer Research (1961) 21:1134-1140.
59. Jacobs PH, Tromovitch TA, Lucasg, Puzak HP: Effect of chloroquine and placebo on warts. Arch Dermatol (1963) 87:89-90.
60. Wilson WW: Clinical evaluation of intralesional administration of hydroxychloroquine sulfate in several diseases. The Southern Medical Journal (1963) 56:794-796.
61. Kimura I: Basic and clinical studies on the treatment of malignant tumors with a fibroblast-inhibiting agent, chloroquine. Nippon Naika Gakkai Zasshi (1963) 52:213-222.
62. Hiraki K, Kimura I: Studies on the treatment of malignant tumors with fibroblast-inhibiting agent. II. Effects of chloroquine on animal tumors. Acta Medicinae Okayama (1963) 17:239-252.
63. Maclean KH, Dorsey FC, Cleveland JL, Kastan MB: Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. J Clin Invest (2008) 118(1):79-88.
64. Rahim R, Strobl JS: Hydroxychloroquine, chloroquine, and all-trans retinoic acid regulate growth, survival, and histone acetylation in breast cancer cells. Anticancer Drugs (2009) 20(8):736-745.
65. Zheng Y, Zhao YL, Deng X, Yang S, Mao Y, Li Z, Jiang P, Zhao X, Wei Y: Chloroquine inhibits colon cancer cell growth in vitro and tumor growth in vivo via induction of apoptosis. Cancer Invest (2009) 27(3):286-292.
66. Amaravadi RK: Autophagy-induced tumor dormancy in ovarian cancer. J Clin Invest (2008) 118(12):3837-3840.
67. Degtyarev M, De Mazière A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, Davis DP et al: Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol (2008) 183(1):101-116.
68. Hu C, Solomon VR, Ulibarri G, Lee H: The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine. Bioorg Med Chem (2008) 16(17):7888-7893.
69. Carew JS, Medina EC, Esquivel JA, Mahalingam D, Swords R, Kelly K, Zhang H, Huang P, Mita AC, Mita MM, Giles FJ et al: Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J Cell Mol Med (2009):doi:10.1111/j.1582-4934.2009.00832.x
70. Fong T, Trinkaus K, Adkins D, Vij R, Devine SM, Tomasson M, Goodnough LT, Lopez S, Graubert T, Shenoy S, Dipersio JF et al: A randomized double-blind trial of hydroxychloroquine for the prevention of chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant (2007) 13(10):1201-1206.
71. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB: Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest (2007) 117(2):326-336.
72. Bellodi C, Lidonnici MR, Hamilton A, Helgason GV, Soliera AR, Ronchetti M, Galavotti S, Young KW, Selmi T, Yacobi R, Van Etten RA et al: Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J Clin Invest (2009) 119(5):1109-1123.
73. Munster T, Gibbs JP, Shen D, Baethge BA, Botstein GR, Caldwell J, Dietz F, Ettlinger R, Golden HE, Lindsley H, McLaughlin GE et al: Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Arthritis Rheum (2002) 46(6):1460-1469.
74. Projean D, Baune B, Farinotti R, Flinois JP, Beaune P, Taburet AM, Ducharme J: In vitro metabolism of chloroquine: Identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation. Drug Metab Dispos (2003) 31(6):748-754.
75. Adedoyin A, Frye RF, Mauro K, Branch RA: Chloroquine modulation of specific metabolizing enzymes activities: Investigation with selective five drug cocktail. Br J Clin Pharmacol (1998) 46(3):215-219. (Pubitemid 28404833)
76. Masimirembwa CM, Hasler JA, Johansson I: Inhibitory effects of antiparasitic drugs on cytochrome P450 2D6. Eur J Clin Pharmacol (1995) 48(1):35-38.
77. Lyons JS, Severns ML: Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of multifocal electroretinography. Am J Ophthalmol (2007) 143(5):801-809.
78. Briceño E, Reyes S, Sotelo J: Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine. Neurosurgical Focus (2003) 14(2):e3.
79. Briceño E, Calderon A, Sotelo J: Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme. Surgical Neurology (2007) 67(4):388-391.
80. Sotelo J, Briceño E, López-González MA: Adding chloroquine to conventional treatment for glioblastoma multiforme: A randomized, double-blind, placebo-controlled trial. Ann Intern Med (2006) 144(5):337-343.
81. Rossi M, Munarriz ER, Bartesaghi S, Milanese M, Dinsdale D, Guerra-Martin MA, Bampton ET, Glynn P, Bonanno G, Knight RA, Nicotera P et al: Desmethylclomipramine induces the accumulation of autophagy markers by blocking autophagic flux. J Cell Sci (2009) 122:3330-3339.
82. Sitia G, Iannacone M, Müller S, Bianchi ME, Guidotti LG: Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice. J Leukoc Biol (2007) 81(1):100-107.
83. Mollica L, De Marchis F, Spitaleri A, Dallacosta C, Pennacchini D, Zamai M, Agresti A, Trisciuoglio L, Musco G, Bianchi ME: Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol (2007) 14(4):431-441.
84. Saïdi H, Melki MT, Gougeon ML: HMGB1-dependent triggering of HIV-1 replication and persistence in dendritic cells as a consequence of NK-DC cross-talk. PLoS ONE (2008) 3(10):e3601.
85. Curtin JF, Liu N, Candolfi M, Xiong W, Assi H, Yagiz K, Edwards MR, Michelsen KS, Kroeger KM, Liu C, Muhammad AK et al: HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med (2009) 6(1):e10.
86. Candolfi M, Yagiz K, Foulad D, Alzadeh GE, Tesarfreund M, Muhammad AK, Puntel M, Kroeger KM, Liu C, Lee S, Curtin JF et al: Release of HMGB1 in response to proapoptotic glioma killing strategies: Efficacy and neurotoxicity. Clin Cancer Res (2009) 15(13):4401-4414.
87. Dong XdaE, Ito N, Lotze MT, Demarco RA, Popovic P, Shand SH, Watkins S, Winikoff S, Brown CK, Bartlett DL, Zeh HJ: High mobility group box I (HMGB1) release from tumor cells after treatment: Implications for development of targeted chemoimmunotherapy. J Immunother (2007) 30(6):596-606.
88. Tang D, Kang R, Xiao W, Zhang H, Lotze MT, Wang H, Xiao X: Quercetin prevents lipopolysaccharide-induced HMGB1 release and proinflammatory function. Am J Respir Cell Mol Biol (2009) 41(6):651-660.
89. Ulloa L, Ochani M, Yang H, Tanovic M, Halperin D, Yang R, Czura CJ, Fink MP, Tracey KJ: Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci USA (2002) 99(19):12351-12356.
90. Lim SC, Choi JE, Kim CH, Duong HQ, Jeong GA, Kang HS, Han SI: Ethyl pyruvate induces necrosis-to-apoptosis switch and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells. Int J Mol Med (2007) 20(2):187-192.
91. Wang Q, Ding Q, Zhou Y, Gou X, Hou L, Chen S, Zhu Z, Xiong L: Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits. Anesthesiology (2009) 110(6): 1279-1286.
92. Yang R, Shaufl AL, Killeen ME, Fink MP: Ethyl pyruvate ameliorates liver injury secondary to severe acute pancreatitis. J Surg Res (2009) 153(2):302-309.
93. Farkas T, Høyer-Hansen M, Jäättelä M: Identification of novel autophagy regulators by a luciferase-based assay for the kinetics of autophagic flux. Autophagy (2009) 5(7):1018-1025.
94. Okamoto K, Kondo-Okamoto N, Ohsumi Y: Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell (2009) 17(1):87-97.
95. Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ: Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell (2009) 17(1):98-109.
96. Qadir MA, Kwok B, Dragowska WH, To KH, Le D, Bally MB, Gorski SM: Macroautophagy inhibition sensitizes tamoxifenresistant breast cancer cells and enhances mitochondrial depolarization. Breast Cancer Res Treat (2008) 112(3):389-403.
97. Moretti L, Kim KW, Jung DK, Willey CD, Lu B: Radiosensitization of solid tumors by z-VAD, a pan-caspase inhibitor. Mol Cancer Ther (2009) 8(5):1270-1279.
98. Apel A, Herr I, Schwarz H, Rodemann HP, Mayer A: Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. Cancer Research (2008) 68(5):1485-1494.
99. Mishima Y, Terui Y, Mishima Y, Taniyama A, Kuniyoshi R, Takizawa T, Kimura S, Ozawa K, Hatake K: Autophagy and autophagic cell death are next targets for elimination of the resistance to tyrosine kinase inhibitors. Cancer Sci (2008) 99(11):2200-2208.
100. Bijnsdorp IV, Peters GJ, Temmink OH, Fukushima M, Kruyt FA: Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5-fluorouracil in colon cancer cells. Int J Cancer (2009):doi:10.1002/ijc.24943
101. Lomonaco SL, Finniss S, Xiang C, Decarvalho A, Umansky F, Kalkanis SN, Mikkelsen T, Brodie C: The induction of autophagy by g-radiation contributes to the radioresistance of glioma stem cells. Int J Cancer (2009) 125(3):717-722.
102. Bilir A, Erguven M, Oktem G, Ozdemir A, Uslu A, Aktas E, Bonavida B: Potentiation of cytotoxicity by combination of imatinib and chlorimipramine in glioma. Int J Oncol (2008) 32(4):829-839.
103. Yang C, Tong Y, Ni W, Liu J, Xu W, Li L, Liu X, Meng H, Qian W: Inhibition of autophagy induced by overexpression of mda-7/interleukin-24 strongly augments the antileukemia activity in vitro and in vivo. Cancer Gene Ther (2009):doi:10.1038/cgt.2009.57.
104. Kim RH, Coates JM, Bowles TL, McNerney GP, Sutcliffe J, Jung JU, Gandour-Edwards R, Chuang FY, Bold RJ, Kung HJ: Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Research (2009) 69(2):700-708.
105. Kim RH, Bold RJ, Kung HJ: ADI, autophagy and apoptosis: Metabolic stress as a therapeutic option for prostate cancer. Autophagy (2009) 5(4):567-568.