Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress

• Autorzy: Huang Y. , Yang W. , Zeng H. , Hu C.
• Języki publikacji: EN

Abstrakty

EN

Upregulation of histone acetylation plays a critical role in the dysregulation of transcription. It alters the structure of chromatin, which leads to the onset of cancer. Histone deacetylase inhibitors may therefore be a promising way to limit cancer progression. In this study, we examined the effects of droxinostat on the growth of HT-29 colon cancer cells. Our results show that droxinostat effectively inhibited cell growth and colony-forming ability by inducing cellular apoptosis and ROS production in HT-29 cells. Notably, the apoptotic inhibitor Z-VAD-FMK significantly decreased the levels of cellular apoptosis and the antioxidant γ-tocotrienol (GT3) significantly decreased ROS production induced by droxinostat treatment. Z-VAD-FMK and GT3 also partially reversed the negative growth effects of droxinstat on HT-29 cells. GT3 treatment decreased cellular apoptosis and increased colony-forming ability upon droxinostat administration. Z-VAD-FMK treatment also partially decreased droxinostat-induced ROS production. Our findings suggest that the effects of droxinostat on colon cancer cells are mediated by the induction of oxidative stress and apoptotic cell death.

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2018
• Tom: 23
• Opis fizyczny: p.1-13,fig.,ref.

Twórcy

autor

Huang Y.

• iangxi provincial key laboratory of preventive medicine, Nanchang University, Nanchang 330006, China 2 Medical School of Nanchang University, 461 Bayi Road, Nanchang 330006, Jiangxi, China

autor

Yang W.

• iangxi provincial key laboratory of preventive medicine, Nanchang University, Nanchang 330006, China 2 Medical School of Nanchang University, 461 Bayi Road, Nanchang 330006, Jiangxi, China

autor

Zeng H.

• iangxi provincial key laboratory of preventive medicine, Nanchang University, Nanchang 330006, China 2 Medical School of Nanchang University, 461 Bayi Road, Nanchang 330006, Jiangxi, China

autor

Hu C.

• iangxi provincial key laboratory of preventive medicine, Nanchang University, Nanchang 330006, China 2 Medical School of Nanchang University, 461 Bayi Road, Nanchang 330006, Jiangxi, China

Bibliografia

• 1. Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW. Colorectal cancer. Lancet. 2005;365:153–65.
• 2. Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi RE, Corcione F. Worldwide burden of colorectal cancer: a review. Updat Surg. 2016;68:7–11.
• 3. McLornan DP, Barrett HL, Cummins R, McDermott U, McDowell C, Conlon SJ, et al. Prognostic significance of TRAIL signaling molecules in stage II and III colorectal cancer. Clin Cancer Res. 2010;16:3442–51.
• 4. Stevenson L, Allen WL, Turkington R, Jithesh PV, Proutski I, Stewart G, et al. Identification of galanin and its receptor GalR1 as novel determinants of resistance to chemotherapy and potential biomarkers in colorectal cancer. Clin Cancer Res. 2012;18:5412–26.
• 5. Galligan L, Longley DB, McEwan M, Wilson TR, McLaughlin K, Johnston PG. Chemotherapy and TRAIL-mediated colon cancer cell death: the roles of p53, TRAIL receptors, and c-FLIP. Mol Cancer Ther. 2005;4:2026–36.
• 6. Pontiki E, Hadjipavlou-Litina D. Histone deacetylase inhibitors (HDACIs). Structure--activity relationships: history and new QSAR perspectives. Eur J Med Chem. 2012;32:1–165.
• 7. Monneret C. Histone deacetylase inhibitors. Eur J Med Chem. 2005;40:1–13.
• 8. Han MH, Park C, Kwon TK, Kim GY, Kim WJ, Hong SH, et al. The Histone Deacetylase Inhibitor Trichostatin A Sensitizes Human Renal Carcinoma Cells to TRAIL-Induced Apoptosis through Down-Regulation of c-FLIPL. Biomol Ther (Seoul). 2015;23:31–8.
• 9. Rao-Bindal K, Koshkina NV, Stewart J, Kleinerman ES. The histone deacetylase inhibitor, MS-275 (entinostat), downregulates c-FLIP, sensitizes osteosarcoma cells to FasL, and induces the regression of osteosarcoma lung metastases. Curr Cancer Drug Targets. 2013;13:411–22.
• 10. Zheng Z, Cheng S, Wu W, Wang L, Zhao Y, Shen Y, et al. c-FLIP is involved in tumor progression of peripheral Tcell lymphoma and targeted by histone deacetylase inhibitors. J Hematol Oncol. 2014;7:88.
• 11. Kauh J, Fan S, Xia M, Yue P, Yang L, Khuri FR, et al. c-FLIP degradation mediates sensitization of pancreatic cancer cells to TRAIL-induced apoptosis by the histone deacetylase inhibitor LBH589. PloS one. 2010;5:e10376.
• 12. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.
• 13. Elrod HA, Lin YD, Yue P, Wang X, Lonial S, Khuri FR, et al. The alkylphospholipid perifosine induces apoptosis of human lung cancer cells requiring inhibition of Akt and activation of the extrinsic apoptotic pathway. Mol Cancer Ther. 2007;6:2029–38.
• 14. Wilson TR, Redmond KM, McLaughlin KM, Crawford N, Gately K, O'Byrne K, et al. Procaspase 8 overexpression in non-small-cell lung cancer promotes apoptosis induced by FLIP silencing. Cell Death Differ. 2009;16:1352–61.
• 15. Rao-Bindal K, Zhou Z, Kleinerman ES. MS-275 sensitizes osteosarcoma cells to Fas ligand-induced cell death by increasing the localization of Fas in membrane lipid rafts. Cell Death Dis. 2012;3:e369.
• 16. Zhao L, Yue P, Khuri FR, Sun SY. mTOR complex 2 is involved in regulation of Cbl-dependent c-FLIP degradation and sensitivity of TRAIL-induced apoptosis. Cancer Res. 2013;73:1946–57.
• 17. Lavrik I, Golks A, Krammer PH. Death receptor signaling. J Cell Sci. 2005;118:265–7.
• 18. Liu X, Yue P, Chen S, Hu L, Lonial S, Khuri FR, et al. The proteasome inhibitor PS-341 (bortezomib) up-regulates DR5 expression leading to induction of apoptosis and enhancement of TRAIL-induced apoptosis despite upregulation of c-FLIP and survivin expression in human NSCLC cells. Cancer Res. 2007;67:4981–8.
• 19. Zhao L, Wen Q, Yang G, Huang Z, Shen T, Li H, et al. Apoptosis induction of dehydrobruceine B on two kinds of human lung cancer cell lines through mitochondrial-dependent pathway. Phytomedicine. 2016;23:114–22.
• 20. Schimmer AD, Thomas MP, Hurren R, Gronda M, Pellecchia M, Pond GR, et al. Identification of small molecules that sensitize resistant tumor cells to tumor necrosis factor-family death receptors. Cancer Res. 2006;66:2367–75.
• 21. Mawji IA, Simpson CD, Hurren R, Gronda M, Williams MA, Filmus J, et al. Critical role for Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein in anoikis resistance and distant tumor formation. J Natl Cancer Inst. 2007;99:811–22.
• 22. Wood TE, Dalili S, Simpson CD, Sukhai MA, Hurren R, Anyiwe K, et al. Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010;9:246–56.
• 23. Kerr E, Holohan C, McLaughlin KM, Majkut J, Dolan S, Redmond K, et al. Identification of an acetylation-dependant Ku70/FLIP complex that regulates FLIP expression and HDAC inhibitor-induced apoptosis. Cell Death Differ. 2012; 19:1317–27.
• 24. Lin Y, Liu X, Yue P, Benbrook DM, Berlin KD, Khuri FR, et al. Involvement of c-FLIP and survivin down-regulation in flexible heteroarotinoid-induced apoptosis and enhancement of TRAIL-initiated apoptosis in lung cancer cells. Mol Cancer Ther. 2008;7:3556–65.
• 25. Sun S, Han Y, Liu J, Fang Y, Tian Y, Zhou J, et al. Trichostatin a targets the mitochondrial respiratory chain, increasing mitochondrial reactive oxygen species production to trigger apoptosis in human breast cancer cells. PLoS One. 2014;9:e91610.
• 26. Ivanova D, Zhelev Z, Aoki I, Bakalova R, Higashi T. Overproduction of reactive oxygen species - obligatory or not for induction of apoptosis by anticancer drugs. Chin J Cancer Res. 2016;28:383–96.
• 27. Buch K, Peters T, Nawroth T, Sanger M, Schmidberger H, Langguth P. Determination of cell survival after irradiation via clonogenic assay versus multiple MTT assay--a comparative study. Radiat Oncol. 2012;7:1.
• 28. McCourt C, Maxwell P, Mazzucchelli R, Montironi R, Scarpelli M, Salto-Tellez M, et al. Elevation of c-FLIP in castrateresistant prostate cancer antagonizes therapeutic response to androgen receptor-targeted therapy. Clin Cancer Res. 2012;18:3822–33.
• 29. Liu J, Li G, Wang X, Wang L, Zhao R, Wang J, et al. Droxinostat, a histone Deacetylase inhibitor, induces apoptosis in hepatocellular carcinoma cell lines via activation of the mitochondrial pathway and Downregulation of FLIP. Transl Oncol. 2016;9:70–8.
• 30. Damaskos C, Garmpis N, Valsami S, Kontos M, Spartalis E, Kalampokas T, et al. Histone Deacetylase inhibitors: an attractive therapeutic strategy against breast Cancer. Anticancer Res. 2017;37(1):35–46.
• 31. Zahnow CA, Topper M, Stone M, Murray-Stewart T, Li H, Baylin S, et al. Inhibitors of DNA methylation, histone Deacetylation, and histone Demethylation: a perfect combination for Cancer therapy. Adv Cancer Res. 2016;130: 55–111.
• 32. Zimmermann KC, Green DR. How cells die: apoptosis pathways. J Allergy Clin Immunol. 2001;108:S99–103.
• 33. Li H, Li C, Shen T, Zhao L, Ren D. R-eriodictyol and S-eriodictyol exhibited comparable effect against H2O2- induced oxidative stress in EA.hy926 cells. Drug Discov Ther. 2014;8:218–24.
• 34. Anantharaju PG, Reddy DB, Padukudru MA, Chitturi CMK, Vimalambike MG, Madhunapantula SV. Induction of colon and cervical cancer cell death by cinnamic acid derivatives is mediated through the inhibition of histone Deacetylases (HDAC). PLoS One. 2017;12:e0186208.
• 35. Shi XY, Ding W, Li TQ, Zhang YX, Zhao SC. Histone Deacetylase (HDAC) inhibitor, Suberoylanilide Hydroxamic acid (SAHA), induces apoptosis in prostate Cancer cell lines via the Akt/FOXO3a signaling pathway. Med Sci Monit. 2017;23:5793–802.
• 36. Ungerstedt JS, Sowa Y, Xu WS, Shao Y, Dokmanovic M, Perez G, et al. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc Natl Acad Sci U S A. 2005;102:673–8.
• 37. Ahrens TD, Timme S, Ostendorp J, Bogatyreva L, Hoeppner J, Hopt UT, et al. Response of esophageal cancer cells to epigenetic inhibitors is mediated via altered thioredoxin activity. Lab Investig. 2016;96:307–16.
• 38. Hendrick E, Peixoto P, Blomme A, Polese C, Matheus N, Cimino J, et al. Metabolic inhibitors accentuate the antitumoral effect of HDAC5 inhibition. Oncogene. 2017;36:4859–74.
• 39. Wasim L, Chopra M. Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells. Biomed Pharmacother. 2016;84:1393–405.

Identyfikatory

DOI

10.1186/s11658-018-0101-5