Valproic acid induces endocytosis-mediated doxorubicin internalization and shows synergistic cytotoxic effects in hepatocellular carcinoma cells

International Journal of Molecular Sciences

Volumn 18, Issue 5, 2017, Pages

  Saha, Subbroto Kumar ^a   Yin, Yingfu ^a   Kim, Kyeongseok ^a   Yang, Gwang Mo ^a   Dayemv, Ahmed Abdal ^a   Choi, Hye Yeon ^a   Cho, Ssang Goo ^a  

^a Konkuk University   (South Korea)

Author keywords

Autophagy; Caveolae endocytosis pathway; Cell death; Doxorubicin; Reactive oxygen species; Valproic acid

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; CASPASE 3; CHLORPROMAZINE; DOXORUBICIN; HISTONE DEACETYLASE; METHYL BETA CYCLODEXTRIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; REACTIVE OXYGEN METABOLITE; VALPROIC ACID; ANTINEOPLASTIC AGENT;

ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGY; CELL VIABILITY; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CYTOTOXICITY; DRUG POTENTIATION; ENDOCYTOSIS; ENZYME ACTIVITY; FLUORESCENCE MICROSCOPY; HEPATOCELLULAR CARCINOMA CELL LINE; HUMAN; HUMAN CELL; IMMUNOCYTOCHEMISTRY; INTERNALIZATION; WESTERN BLOTTING; DRUG EFFECTS; HEP-G2 CELL LINE; LIVER CELL CARCINOMA; LIVER TUMOR; METABOLISM;

ANTINEOPLASTIC AGENTS; APOPTOSIS; AUTOPHAGY; CARCINOMA, HEPATOCELLULAR; CASPASE 3; DOXORUBICIN; DRUG SYNERGISM; ENDOCYTOSIS; HEP G2 CELLS; HUMANS; LIVER NEOPLASMS; POLY(ADP-RIBOSE) POLYMERASES; REACTIVE OXYGEN SPECIES; VALPROIC ACID;

EID: 85019241724     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms18051048     Document Type: Article

References (80)

1. WHO. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012; International Agency for Research on Cancer: Lyon, France, 2014.
2. Attwa, M.H.; El-Etreby, S.A. Guide for diagnosis and treatment of hepatocellular carcinoma. World J. Hepatol. 2015, 7, 1632–1651.
3. Smith, L.; Watson, M.B.; O’Kane, S.L.; Drew, P.J.; Lind, M.J.; Cawkwell, L. The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays. Mol. Cancer Ther. 2006, 5, 2115–2120.
4. Rashid, S.; Ali, N.; Nafees, S.; Ahmad, S.T.; Arjumand, W.; Hasan, S.K.; Sultana, S. Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats. Toxicol. Mech. Methods 2013, 23, 337–345.
5. Rai, G.; Mishra, S.; Suman, S.; Shukla, Y. Resveratrol improves the anticancer effects of doxorubicin in vitro and in vivo models: A mechanistic insight. Phytomedicine 2016, 23, 233–242.
6. Cao, H.; Phan, H.; Yang, L.X. Improved chemotherapy for hepatocellular carcinoma. Anticancer Res. 2012, 32, 1379–86.
7. Yeo, W.; Mok, T.S.; Zee, B.; Leung, T.W.; Lai, P.B.; Lau, W.Y.; Koh, J.; Mo, F.K.; Yu, S.C.; Chan, A.T.; et al. A randomized phase III study of doxorubicin versus cisplatin/interferon α-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J. Natl. Cancer Inst. 2005, 97, 1532–1538.
8. Fan, L.L.; Song, B.; Sun, G.P.; Ma, T.; Zhong, F.; Wei, W. Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells. PLoS ONE 2013, 8, e62627.
9. Xiang, Q.F.; Zhang, D.M.; Wang, J.N.; Zhang, H.W.; Zheng, Z.Y.; Yu, D.C.; Li, Y.J.; Xu, J.; Chen, Y.J.; Shang, C.Z. Cabozantinib reverses multidrug resistance of human hepatoma HepG2/adr cells by modulating the function of P-glycoprotein. Liver Int. 2015, 35, 1010–1023.
10. Zhou, J.; Wan, B.; Liu, X.M.; Li, R.W.; Wang, Y.L.; Yu, L. MK5 is degraded in response to doxorubicin and negatively regulates doxorubicin-induced apoptosis in hepatocellular carcinoma cells. Biochem. Biophys. Res. Commun. 2012, 427, 581–586.
11. Jung, E.U.; Yoon, J.H.; Lee, Y.J.; Lee, J.H.; Kim, B.H.; Yu, S.J.; Myung, S.J.; Kim, Y.J.; Lee, H.S. Hypoxia and retinoic acid-inducible NDRG1 expression is responsible for doxorubicin and retinoic acid resistance in hepatocellular carcinoma cells. Cancer Lett. 2010, 298, 9–15.
12. Thakur, J.S.; Chauhan, C.G.; Diwana, V.K.; Chauhan, D.C.; Thakur, A. Extravasational side effects of cytotoxic drugs: A preventable catastrophe. Indian J. Plast. Surg. 2008, 41, 145–150.
13. Perucca, E. Pharmacological and therapeutic properties of valproate: A summary after 35 years of clinical experience. CNS Drugs 2002, 16, 695–714.
14. Carriere, C.H.; Kang, N.H.; Niles, L.P. Neuroprotection by valproic acid in an intrastriatal rotenone model of Parkinson’s disease. Neuroscience 2014, 267, 114–121.
15. Hu, J.P.; Xie, J.W.; Wang, C.Y.; Wang, T.; Wang, X.; Wang, S.L.; Teng, W.P.; Wang, Z.Y. Valproate reduces tau phosphorylation via cyclin-dependent kinase 5 and glycogen synthase kinase 3 signaling pathways. Brain Res. Bull. 2011, 85, 194–200.
16. Penas, C.; Verdu, E.; Asensio-Pinilla, E.; Guzman-Lenis, M.S.; Herrando-Grabulosa, M.; Navarro, X.; Casas, C. Valproate reduces CHOP levels and preserves oligodendrocytes and axons after spinal cord injury. Neuroscience 2011, 178, 33–44.
17. Yi, J.; Zhang, L.; Tang, B.; Han, W.; Zhou, Y.; Chen, Z.; Jia, D.; Jiang, H. Sodium valproate alleviates neurodegeneration in SCA3/MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4. PLoS ONE 2013, 8, e54792.
18. Schmid, M.M.; Freudenmann, R.W.; Keller, F.; Connemann, B.J.; Hiemke, C.; Gahr, M.; Kratzer, W.; Fuchs, M.; Schonfeldt-Lecuona, C. Non-fatal and fatal liver failure associated with valproic acid. Pharmacopsychiatry 2013, 46, 63–68.
19. Silva, M.F.; Aires, C.C.; Luis, P.B.; Ruiter, J.P.; IJlst, L.; Duran, M.; Wanders, R.J.; Tavares de Almeida, I. Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: A review. J. Inherit. Metab. Dis. 2008, 31, 205–216.
20. Nie, D.; Huang, K.; Yin, S.; Li, Y.; Xie, S.; Ma, L.; Wang, X.; Wu, Y.; Xiao, J. Synergistic/additive interaction of valproic acid with bortezomib on proliferation and apoptosis of acute myeloid leukemia cells. Leuk. Lymphoma 2012, 53, 2487–2495.
21. Sidana, A.; Wang, M.; Shabbeer, S.; Chowdhury, W.H.; Netto, G.; Lupold, S.E.; Carducci, M.; Rodriguez, R. Mechanism of growth inhibition of prostate cancer xenografts by valproic acid. J. Biomed. Biotechnol. 2012, 2012, 180363.
22. Xie, C.; Edwards, H.; Lograsso, S.B.; Buck, S.A.; Matherly, L.H.; Taub, J.W.; Ge, Y. Valproic acid synergistically enhances the cytotoxicity of clofarabine in pediatric acute myeloid leukemia cells. Pediatr. Blood Cancer 2012, 59, 1245–1251.
23. Yamauchi, Y.; Izumi, Y.; Asakura, K.; Fukutomi, T.; Serizawa, A.; Kawai, K.; Wakui, M.; Suematsu, M.; Nomori, H. Lovastatin and valproic acid additively attenuate cell invasion in ACC-MESO-1 cells. Biochem. Biophys. Res. Commun. 2011, 410, 328–332.
24. Li, X.; Zhu, Y.; He, H.; Lou, L.; Ye, W.; Chen, Y.; Wang, J. Synergistically killing activity of aspirin and histone deacetylase inhibitor valproic acid (VPA) on hepatocellular cancer cells. Biochem. Biophys. Res. Commun. 2013, 436, 259–264.
25. Machado, M.C.; Bellodi-Privato, M.; Kubrusly, M.S.; Molan, N.A.; Tharcisio, T., Jr.; de Oliveira, E.R.; D’Albuquerque, L.A. Valproic acid inhibits human hepatocellular cancer cells growth in vitro and in vivo. J. Exp. Ther. Oncol. 2011, 9, 85–92.
26. Tatebe, H.; Shimizu, M.; Shirakami, Y.; Sakai, H.; Yasuda, Y.; Tsurumi, H.; Moriwaki, H. Acyclic retinoid synergises with valproic acid to inhibit growth in human hepatocellular carcinoma cells. Cancer Lett. 2009, 285, 210–217.
27. Gottlicher, M.; Minucci, S.; Zhu, P.; Kramer, O.H.; Schimpf, A.; Giavara, S.; Sleeman, J.P.; Lo Coco, F.; Nervi, C.; Pelicci, P.G.; et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 2001, 20, 6969–6978.
28. Miyatake, M.; Kuno, T.; Kita, A.; Katsura, K.; Takegawa, K.; Uno, S.; Nabata, T.; Sugiura, R. Valproic acid affects membrane trafficking and cell-wall integrity in fission yeast. Genetics 2007, 175, 1695–1705.
29. Xu, X.H.; Muller-Taubenberger, A.; Adley, K.E.; Pawolleck, N.; Lee, V.W.Y.; Wiedemann, C.; Sihra, T.S.; Maniak, M.; Jin, T.; Williams, R.S.B. Attenuation of phospholipid signaling provides a novel mechanism for the action of valproic acid. Eukaryot. Cell 2007, 6, 899–906.
30. Elphick, L.M.; Pawolleck, N.; Guschina, I.A.; Chaieb, L.; Eikel, D.; Nau, H.; Harwood, J.L.; Plant, N.J.; Williams, R.S.B. Conserved valproic-acid-induced lipid droplet formation in Dictyostelium and human hepatocytes identifies structurally active compounds. Dis. Model. Mech. 2012, 5, 231–240.
31. Cowles, C.R.; Emr, S.D.; Horazdovsky, B.F. Mutations in the vps45 gene, a Sec1 homologue, result in vacuolar protein sorting defects and accumulation of membrane vesicles. J. Cell Sci. 1994, 107, 3449–3459.
32. Bryant, N.J.; Piper, R.C.; Gerrard, S.R.; Stevens, T.H. Traffic into the prevacuolar/endosomal compartment of Saccharomyces cerevisiae: A vps45-dependent intracellular route and a vps45-independent, endocytic route. Eur. J. Cell Biol. 1998, 76, 43–52.
33. Selkoe, D.J. Showing transmitters the door: Synucleins accelerate vesicle release. Nat. Neurosci. 2017, 20, 629–631.
34. Schreij, A.M.A.; Fon, E.A.; McPherson, P.S. Endocytic membrane trafficking and neurodegenerative disease. Cell Mol. Life Sci. 2016, 73, 1529–1545.
35. Li, X.; Garrity, A.G.; Xu, H. Regulation of membrane trafficking by signalling on endosomal and lysosomal membranes. J. Pphysiol. 2013, 591, 4389–4401.
36. Mazzolini, J.; Weber, R.J.; Chen, H.-S.; Khan, A.; Guggenheim, E.; Shaw, R.K.; Chipman, J.K.; Viant, M.R.; Rappoport, J.Z. Protein corona modulates uptake and toxicity of nanoceria via clathrin-mediated endocytosis. Biol. Bull. 2016, 231, 40–60.
37. Maes, H.; Olmeda, D.; Soengas, M.S.; Agostinis, P. Vesicular trafficking mechanisms in endothelial cells as modulators of the tumor vasculature and targets of antiangiogenic therapies. FEBS J. 2016, 283, 25–38.
38. Zhang, L.; Yang, X.; Lv, Y.; Xin, X.; Qin, C.; Han, X.; Yang, L.; He, W.; Yin, L. Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer. Sci. Rep. 2017, 7, 46186.
39. Chen, C.-L.; Yang, P.-H.; Kao, Y.-C.; Chen, P.-Y.; Chung, C.-L.; Wang, S.-W. Pentabromophenol suppresses TGF-β signaling by accelerating degradation of type II TGF-β receptors via caveolae-mediated endocytosis. Sci. Rep. 2017, 7, 43206.
40. Du, J.Z.; Du, X.J.; Mao, C.Q.; Wang, J. Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. J. Am. Chem. Soc. 2011, 133, 17560–17563.
41. Wang, F.; Wang, Y.C.; Dou, S.; Xiong, M.H.; Sun, T.M.; Wang, J. Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. ACS Nano 2011, 5, 3679–3692.
42. Thao, L.Q.; Lee, C.; Kim, B.; Lee, S.; Kim, T.H.; Kim, J.O.; Lee, E.S.; Oh, K.T.; Choi, H.G.; Yoo, S.D.; Youn, Y.S.; et al. Doxorubicin and paclitaxel co-bound lactosylated albumin nanoparticles having targetability to hepatocellular carcinoma. Colloids Surf. B Biointerfaces 2017, 152, 183–191.
43. Herzog, A.G.; Farina, E.L.; Blum, A.S. Serum valproate levels with oral contraceptive use. Epilepsia 2005, 46, 970–971.
44. Hao, J.Q.; Li, Q.; Xu, S.P.; Shen, Y.X.; Sun, G.Y. Effect of lumiracoxib on proliferation and apoptosis of human nonsmall cell lung cancer cells in vitro. Chin. Med. J. 2008, 121, 602–607.
45. Zhang, J.; Yi, M.; Zha, L.; Chen, S.; Li, Z.; Li, C.; Gong, M.; Deng, H.; Chu, X.; Chen, J.; et al. Sodium butyrate induces endoplasmic reticulum stress and autophagy in colorectal cells: Implications for apoptosis. PLoS ONE 2016, 11, e0147218.
46. Cai, S.; Alhowyan, A.A.; Yang, Q.; Forrest, W.C.; Shnayder, Y.; Forrest, M.L. Cellular uptake and internalization of hyaluronan-based doxorubicin and cisplatin conjugates. J. Drug Target. 2014, 22, 648–657.
47. Majumdar, S.; Tejo, B.A.; Badawi, A.H.; Moore, D.; Krise, J.P.; Siahaan, T.J. Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60. Mol. Pharm. 2009, 6, 396–406.
48. Marsh, M.; McMahon, H.T. The structural era of endocytosis. Science 1999, 285, 215–220.
49. Mukherjee, S.; Ghosh, R.N.; Maxfield, F.R. Endocytosis. Physiol. Rev. 1997, 77, 759–803.
50. Hao, X.; Wu, J.; Shan, Y.; Cai, M.; Shang, X.; Jiang, J.; Wang, H. Caveolae-mediated endocytosis of biocompatible gold nanoparticles in living Hela cells. J. Phys. Condens. Matter 2012, 24, 164207.
51. Bruix, J.; Raoul, J.L.; Sherman, M.; Mazzaferro, V.; Bolondi, L.; Craxi, A.; Galle, P.R.; Santoro, A.; Beaugrand, M.; Sangiovanni, A.; et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. J. Hepatol. 2012, 57, 821–829.
52. Catalano, M.G.; Fortunati, N.; Pugliese, M.; Poli, R.; Bosco, O.; Mastrocola, R.; Aragno, M.; Boccuzzi, G. Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells. J. Endocrinol. 2006, 191, 465–472.
53. Kim, T.H.; Yoo, Y.H.; Kang, D.Y.; Suh, H.; Park, M.K.; Park, K.J.; Kim, S.H. Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin. Int. J. Oncol. 2009, 34, 1353–1362.
54. Rho, J.H.; Kang, D.Y.; Park, K.J.; Choi, H.J.; Lee, H.S.; Yee, S.B.; Yoo, Y.H. Doxorubicin induces apoptosis with profile of large-scale DNA fragmentation and without DNA ladder in anaplastic thyroid carcinoma cells via histone hyperacetylation. Int. J. Oncol. 2005, 27, 465–471.
55. Kwak, M.S.; Yu, S.J.; Yoon, J.H.; Lee, S.H.; Lee, S.M.; Lee, J.H.; Kim, Y.J.; Lee, H.S.; Kim, C.Y. Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo hepatocellular carcinoma model. J. Cancer Res. Clin. Oncol. 2015, 141, 2037–2045.
56. Wang, D.; Jing, Y.; Ouyang, S.; Liu, B.; Zhu, T.; Niu, H.; Tian, Y. Inhibitory effect of valproic acid on bladder cancer in combination with chemotherapeutic agents in vitro and in vivo. Oncol. Lett. 2013, 6, 1492–1498.
57. Eot-Houllier, G.; Fulcrand, G.; Magnaghi-Jaulin, L.; Jaulin, C. Histone deacetylase inhibitors and genomic instability. Cancer Lett. 2009, 274, 169–176.
58. Han, B.R.; You, B.R.; Park, W.H. Valproic acid inhibits the growth of Hela cervical cancer cells via caspase-dependent apoptosis. Oncol. Rep. 2013, 30, 2999–3005.
59. Ji, M.M.; Wang, L.; Zhan, Q.; Xue, W.; Zhao, Y.; Zhao, X.; Xu, P.P.; Shen, Y.; Liu, H.; Janin, A.; et al. Induction of autophagy by valproic acid enhanced lymphoma cell chemosensitivity through HDAC-independent and IP3-mediated PRKAA activation. Autophagy 2015, 11, 2160–2171.
60. 2+ in human cardiac progenitor cells. Int. J. Mol. Sci. 2016, 17, 1680.
61. Ungerstedt, J.S.; Sowa, Y.; Xu, W.S.; Shao, Y.; Dokmanovic, M.; Perez, G.; Ngo, L.; Holmgren, A.; Jiang, X.; Marks, P.A. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc. Natl. Acad. Sci. USA 2005, 102, 673–678.
62. Xia, Q.; Zheng, Y.; Jiang, W.; Huang, Z.; Wang, M.; Rodriguez, R.; Jin, X. Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells. Oncol. Lett. 2016, 12, 1826–1832.
63. 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 Res. 2001, 61, 439–444.
64. Graziani, G.; Tentori, L.; Portarena, I.; Vergati, M.; Navarra, P. Valproic acid increases the stimulatory effect of estrogens on proliferation of human endometrial adenocarcinoma cells. Endocrinology 2003, 144, 2822–2828.
65. Takai, N.; Desmond, J.C.; Kumagai, T.; Gui, D.; Said, J.W.; Whittaker, S.; Miyakawa, I.; Koeffler, H.P. Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin. Cancer Res. 2004, 10, 1141–1149.
66. Catalano, M.G.; Pugliese, M.; Gallo, M.; Brignardello, E.; Milla, P.; Orlandi, F.; Limone, P.P.; Arvat, E.; Boccuzzi, G.; Piovesan, A. Valproic acid, a histone deacetylase inhibitor, in combination with paclitaxel for anaplastic thyroid cancer: Results of a multicenter randomized controlled phase II/III trial. Int. J. Endocrinol. 2016, 2016, 2930414.
67. Kwiecinska, P.; Tauboll, E.; Grzyb, E.; Fiedor, E.; Ptak, A.; Gregoraszczuk, E.L. Valproic acid as a promising co-treatment with paclitaxel and doxorubicin in different ovarian carcinoma cell lines. Int. J. Gynecol. Cancer 2016, 26, 1546–1556.
68. Tarasenko, N.; Cutts, S.M.; Phillips, D.R.; Berkovitch-Luria, G.; Bardugo-Nissim, E.; Weitman, M.; Nudelman, A.; Rephaeli, A. A novel valproic acid prodrug as an anticancer agent that enhances doxorubicin anticancer activity and protects normal cells against its toxicity in vitro and in vivo. Biochem. Pharmacol. 2014, 88, 158–168.
69. Ververis, K.; Rodd, A.L.; Tang, M.M.; El-Osta, A.; Karagiannis, T.C. Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes. Cell Mol. Life Sci. 2011, 68, 4101–4114.
70. Rejman, J.; Oberle, V.; Zuhorn, I.S.; Hoekstra, D. Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis. Biochem. J. 2004, 377, 159–169.
71. Yao, W.; Li, K.; Liao, K. Macropinocytosis contributes to the macrophage foam cell formation in RAW264.7 cells. Acta Biochim. Biophys. Sin. 2009, 41, 773–780.
72. Rauniyar, N.; Subramanian, K.; Lavallée-Adam, M.; Martínez-Bartolomé, S.; Balch, W.E.; Yates, J.R. Quantitative proteomics of human fibroblasts with I1061T mutation in Niemann-Pick C1 (NPC1) protein provides insights into the disease pathogenesis. Mol. Cell. Proteom. 2015, 14, 1734–1749.
73. Rodal, S.K.; Skretting, G.; Garred, O.; Vilhardt, F.; van Deurs, B.; Sandvig, K. Extraction of cholesterol with methyl-β-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol. Biol. Cell 1999, 10, 961–974.
74. Liu, B.; Li, H.; Repa, J.J.; Turley, S.D.; Dietschy, J.M. Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J. Lipid Res. 2008, 49, 663–669.
75. Dayem, A.A.; Kim, B.; Gurunathan, S.; Choi, H.Y.; Yang, G.; Saha, S.K.; Han, D.; Han, J.; Kim, K.; Kim, J.H.; et al. Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways. Biotechnol. J. 2014, 9, 934–943.
76. Mizuno, S.; Yasuo, M.; Bogaard, H.J.; Kraskauskas, D.; Natarajan, R.; Voelkel, N.F. Inhibition of histone deacetylase causes emphysema. Am. J. Physiol. Lung C 2011, 300, 402–413.
77. Pitchaimani, A.; Renganathan, A.; Cinthaikinian, S.; Premkumar, K. Photochemotherapeutic effects of UV-C on acridine orange in human breast cancer cells: Potential application in anticancer therapy. RSC Adv. 2014, 4, 22123–22128.
78. Saha, S.K.; Choi, H.Y.; Kim, B.W.; Dayem, A.A.; Yang, G.M.; Kim, K.S.; Yin, Y.F.; Cho, S.G. KRT19 directly interacts with β-catenin/RAC1 complex to regulate NUMB-dependent NOTCH signaling pathway and breast cancer properties. Oncogene 2017, 36, 332–349.
79. Arthur, C.R.; Gupton, J.T.; Kellogg, G.E.; Yeudall, W.A.; Cabot, M.C.; Newsham, I.F.; Gewirtz, D.A. Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03-14, a novel microtubule poison. Biochem. Pharmacol. 2007, 74, 981–991.
80. Hu, Q.; Sun, W.; Qian, C.; Wang, C.; Bomba, H.N.; Gu, Z. Anticancer platelet-mimicking nanovehicles. Adv. Mater. 2015, 27, 7043–7050.