dev exp health med

Developments and Experiments in Health and Medicine

3062-2948

Dokuz Eylul University

10.18614/dehm.1751132

Clinical Oncology

Klinik Onkoloji

Investigation of the epigenetic response to the apoptotic effect of caspase-3 in colon cancer cell line (HT-29)

https://orcid.org/0000-0002-9777-5173

Gurbuz Can

Venhar

KARABÜK ÜNİVERSİTESİ

07 25 2025

39 3 179 188 02 19 2025 06 12 2025

2025

Developments and Experiments in Health and Medicine

BACKGROUNDColorectal cancer represents the third most prevalent cause of cancer-related fatalities, attributable to its high rate of recurrence and mounting resistance to existing therapeutic interventions. The objective of this study was to undertake a comparative analysis of caspase-3, HDAC1 and HDAC2 gene expression levels in HUVEC and HT-29 cells, with a view to elucidating the interplay between apoptotic and epigenetic mechanisms.METHODSThe study was conducted by culturing the HT-29 and HUVEC cell lines under appropriate conditions and performing real-time PCR to measure the gene expression levels of caspase-3, HDAC1, and HDAC2 in the cells.RESULTSThe results obtained revealed a high level of caspase-3 activity and a low levels of HDAC1 and HDAC2 activity in the HUVEC cells.In contrast, a low level of caspase-3 activity and high levels of HDAC1 and HDAC2 activity were detected in the HT-29 cells.CONCLUSIONIn conclusion, the present study demonstrated that the epigenetic response to the apoptotic effect of caspase-3 in the colon cancer cell line (HT-29) and the HUVEC cell line was found to be associated with a negative correlation, suggesting that these genes may serve as potential biomarkers for colon cancer diagnosis and treatment.

Caspase-3 colon cancer HT-29 HDAC1 HDAC2 HUVEC

1. Dupont C, Armant DR, Brenner CA. Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med. 2009;27(5):351-7.

2. Bayat S, Shekari Khaniani M, Choupani J, Alivand MR, Mansoori Derakhshan S. HDACis (class I), cancer stem cell, and phytochemicals: Cancer therapy and prevention implications. Biomedicine & Pharmacotherapy. 2018;97:1445-53.

3. Hsu Y-F, Sheu J-R, Lin C-H, Yang D-S, Hsiao G, Ou G, et al. Trichostatin A and sirtinol suppressed survivin expression through AMPK and p38MAPK in HT29 colon cancer cells. Biochimica et Biophysica Acta (BBA) - General Subjects. 2012;1820(2):104-15.

4. Ropero S, Esteller M. The role of histone deacetylases (HDACs) in human cancer. Mol Oncol. 2007;1(1):19-25.

5. Krishnan M, Singh AB, Smith JJ, Sharma A, Chen X, Eschrich S, et al. HDAC inhibitors regulate claudin-1 expression in colon cancer cells through modulation of mRNA stability. Oncogene. 2010;29(2):305-12.

6. Liang T, Wang F, Elhassan RM, Cheng Y, Tang X, Chen W, et al. Targeting histone deacetylases for cancer therapy: Trends and challenges. Acta Pharmaceutica Sinica B. 2023;13(6):2425-63.

7. Zhou M, Liu X, Li Z, Huang Q, Li F, Li CY. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer. 2018;143(4):921-30.

8. Zhu C, Fan F, Li C-Y, Xiong Y, Liu X. Caspase-3 promotes oncogene-induced malignant transformation via EndoG-dependent Src-STAT3 phosphorylation. Cell Death & Disease. 2024;15(7):486.

9. Zhu P, Martin E, Mengwasser J, Schlag P, Janssen K-P, Göttlicher M. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell. 2004;5(5):455-63.

10. Chen QW, Zhu XY, Li YY, Meng ZQ. Epigenetic regulation and cancer (Review). Oncol Rep. 2014;31(2):523-32.

11. Li Z, Zhu W-G. Targeting Histone Deacetylases for Cancer Therapy: From Molecular Mechanisms to Clinical Implications. International Journal of Biological Sciences. 2014;10(7):757-70.

12. Zhang B, Liu B, Chen D, Setroikromo R, Haisma HJ, Quax WJ. Histone Deacetylase Inhibitors Sensitize TRAIL-Induced Apoptosis in Colon Cancer Cells. Cancers. 2019;11(5):645.

13. Wilson AJ, Byun DS, Popova N, Murray LB, L'Italien K, Sowa Y, et al. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem. 2006;281(19):13548-58.

14. Ishihama K, Yamakawa M, Semba S, Takeda H, Kawata S, Kimura S, Kimura W. Expression of HDAC1 and CBP/p300 in human colorectal carcinomas. J Clin Pathol. 2007;60(11):1205-10.

15. Yang H, Salz T, Zajac-Kaye M, Liao D, Huang S, Qiu Y. Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators. Faseb j. 2014;28(10):4265-79.

16. Min KN, Joung KE, Kim DK, Sheen YY. Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer. Environ Health Toxicol. 2012;27:e2012010.

17. Patra S, Panigrahi DP, Praharaj PP, Bhol CS, Mahapatra KK, Mishra SR, et al. Dysregulation of histone deacetylases in carcinogenesis and tumor progression: a possible link to apoptosis and autophagy. Cellular and Molecular Life Sciences. 2019;76(17):3263-82.

18. Portanova P, Russo T, Pellerito O, Calvaruso G, Giuliano M, Vento R, Tesoriere G. The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells. Int J Oncol. 2008;33(2):325-31.

19. Sohaib M, Ezhilarasan D. Carbamazepine, a Histone Deacetylase Inhibitor Induces Apoptosis in Human Colon Adenocarcinoma Cell Line HT-29. J Gastrointest Cancer. 2020;51(2):564-70.

20. Tsai F-L, Huang H-L, Lai M-J, Liou J-P, Pan S-L, Yang C-R. Anticancer Study of a Novel Pan-HDAC Inhibitor MPT0G236 in Colorectal Cancer Cells. International Journal of Molecular Sciences. 2023;24(16):12588.

21. Jo YK, Park NY, Shin JH, Jo DS, Bae JE, Choi ES, et al. Up-regulation of UVRAG by HDAC1 Inhibition Attenuates 5FU-induced Cell Death in HCT116 Colorectal Cancer Cells. Anticancer Res. 2018;38(1):271-7.