DNA Methylation and Apoptosis Resistance in Cancer Cells

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2014 Apr 9

PMID 24709797

Citations 37

Authors

Eric Hervouet

Mathilde Cheray

Francois Marie Vallette

Pierre-Francois Cartron

Affiliations

Soon will be listed here.

Abstract

Apoptosis is a cell death programme primordial to cellular homeostasis efficiency. This normal cell suicide program is the result of the activation of a cascade of events in response to death stimuli. Apoptosis occurs in normal cells to maintain a balance between cell proliferation and cell death. A deregulation of this balance due to modifications in the apoptosic pathway leads to different human diseases including cancers. Apoptosis resistance is one of the most important hallmarks of cancer and some new therapeutical strategies focus on inducing cell death in cancer cells. Nevertheless, cancer cells are resistant to treatment inducing cell death because of different mechanisms, such as DNA mutations in gene coding for pro-apoptotic proteins, increased expression of anti-apoptotic proteins and/or pro-survival signals, or pro-apoptic gene silencing mediated by DNA hypermethylation. In this context, aberrant DNA methylation patterns, hypermethylation and hypomethylation of gene coding for proteins implicated in apoptotic pathways are possible causes of cancer cell resistance. This review highlights the role of DNA methylation of apoptosis-related genes in cancer cell resistance.

Citing Articles

Synergistic Neuroprotection Through Epigenetic Modulation by Combined Curcumin-Enriched Turmeric Extract and L-Ascorbic Acid in Oxidative Stress-Induced SH-SY5Y Cell Damage.

Khongrum J, Mairuae N, Thanchomnang T, Zhang M, Bai G, Palachai N Foods. 2025; 14(5).

PMID: 40077595 PMC: 11898916. DOI: 10.3390/foods14050892.

Aberrant DNA methylation as a key modulator of cell death pathways: insights into cancer progression and other diseases.

Zahoor A, Khazer R, Mehraj I, Gani U, Fayaz F, Khanday F Funct Integr Genomics. 2025; 25(1):50.

PMID: 40024973 DOI: 10.1007/s10142-025-01552-x.

Environmental Implication of Herbicide Use.

Bacmaga M, Wyszkowska J, Kucharski J Molecules. 2025; 29(24.

PMID: 39770054 PMC: 11677524. DOI: 10.3390/molecules29245965.

Selective Estrogen Receptor Modulators' (SERMs) Influence on Expression in Breast Cancer Cell Lines with Distinct Biological Subtypes.

Linowiecka K, Szpotan J, Godlewska M, Gawel D, Zarakowska E, Gackowski D Int J Mol Sci. 2024; 25(16).

PMID: 39201247 PMC: 11354732. DOI: 10.3390/ijms25168561.

Cancer cells same as zombies reprogram normal cells via the secreted microenvironment.

Rabiee S, Hoveizi E, Barati M, Salehzadeh A, Joghataei M, Tavakol S PLoS One. 2023; 18(7):e0288003.

PMID: 37506087 PMC: 10381049. DOI: 10.1371/journal.pone.0288003.

References

Guan X, Sagara J, Yokoyama T, Koganehira Y, Oguchi M, Saida T . ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma. Int J Cancer. 2003; 107(2):202-8. DOI: 10.1002/ijc.11376. View

Friedrich M, Weisenberger D, Cheng J, Chandrasoma S, Siegmund K, Gonzalgo M . Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin Cancer Res. 2004; 10(22):7457-65. DOI: 10.1158/1078-0432.CCR-04-0930. View

Byun D, Cho K, Ryu B, Lee M, Kang M, Kim H . Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas. Cancer Res. 2003; 63(21):7068-75. View

Horak P, Pils D, Haller G, Pribill I, Roessler M, Tomek S . Contribution of epigenetic silencing of tumor necrosis factor-related apoptosis inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer. Mol Cancer Res. 2005; 3(6):335-43. DOI: 10.1158/1541-7786.MCR-04-0136. View

Terasawa K, Sagae S, Toyota M, Tsukada K, Ogi K, Satoh A . Epigenetic inactivation of TMS1/ASC in ovarian cancer. Clin Cancer Res. 2004; 10(6):2000-6. DOI: 10.1158/1078-0432.ccr-0932-03. View

Obata T, Toyota M, Satoh A, Sasaki Y, Ogi K, Akino K . Identification of HRK as a target of epigenetic inactivation in colorectal and gastric cancer. Clin Cancer Res. 2003; 9(17):6410-8. View

Lee M, Huh J, Chung S, Lee J, Byun D, Ryu B . Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses. Oncogene. 2006; 25(42):5807-22. DOI: 10.1038/sj.onc.1209867. View

Wu J, Wood G . Reduction of Fas/CD95 promoter methylation, upregulation of Fas protein, and enhancement of sensitivity to apoptosis in cutaneous T-cell lymphoma. Arch Dermatol. 2010; 147(4):443-9. DOI: 10.1001/archdermatol.2010.376. View

Garrison S, Jeffers J, Yang C, Nilsson J, Hall M, Rehg J . Selection against PUMA gene expression in Myc-driven B-cell lymphomagenesis. Mol Cell Biol. 2008; 28(17):5391-402. PMC: 2519737. DOI: 10.1128/MCB.00907-07. View

10.

Liu F, Liu Q, Yang D, Bollag W, Robertson K, Wu P . Verticillin A overcomes apoptosis resistance in human colon carcinoma through DNA methylation-dependent upregulation of BNIP3. Cancer Res. 2011; 71(21):6807-16. PMC: 3206150. DOI: 10.1158/0008-5472.CAN-11-1575. View

11.

Stone A, Bobo W, Brat D, Devi N, Van Meir E, Vertino P . Aberrant methylation and down-regulation of TMS1/ASC in human glioblastoma. Am J Pathol. 2004; 165(4):1151-61. PMC: 1618625. DOI: 10.1016/S0002-9440(10)63376-7. View

12.

Pulling L, Grimes M, Damiani L, Juri D, Do K, Tellez C . Dual promoter regulation of death-associated protein kinase gene leads to differentially silenced transcripts by methylation in cancer. Carcinogenesis. 2009; 30(12):2023-30. PMC: 2792322. DOI: 10.1093/carcin/bgp276. View

13.

Saito Y, Jones P . Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle. 2006; 5(19):2220-2. DOI: 10.4161/cc.5.19.3340. View

14.

Suzuki M, Shigematsu H, Shivapurkar N, Reddy J, Miyajima K, Takahashi T . Methylation of apoptosis related genes in the pathogenesis and prognosis of prostate cancer. Cancer Lett. 2006; 242(2):222-30. DOI: 10.1016/j.canlet.2005.11.002. View

15.

Teitz T, Wei T, Valentine M, Vanin E, Grenet J, Valentine V . Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat Med. 2000; 6(5):529-35. DOI: 10.1038/75007. View

16.

Kong W, Zhang S, Guo C, Wang Y, Chen X, Zhang S . Effect of methylation-associated silencing of the death-associated protein kinase gene on nasopharyngeal carcinoma. Anticancer Drugs. 2006; 17(3):251-9. DOI: 10.1097/00001813-200603000-00003. View

17.

Hermeking H . The miR-34 family in cancer and apoptosis. Cell Death Differ. 2009; 17(2):193-9. DOI: 10.1038/cdd.2009.56. View

18.

Fabiani E, Leone G, Giachelia M, DAlo F, Greco M, Criscuolo M . Analysis of genome-wide methylation and gene expression induced by 5-aza-2'-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia. Leuk Lymphoma. 2010; 51(12):2275-84. DOI: 10.3109/10428194.2010.528093. View

19.

Zou B, Chim C, Zeng H, Leung S, Yang Y, Tu S . Correlation between the single-site CpG methylation and expression silencing of the XAF1 gene in human gastric and colon cancers. Gastroenterology. 2006; 131(6):1835-43. DOI: 10.1053/j.gastro.2006.09.050. View

20.

Chung S, Lee M, Ryu B, Lee J, Han J, Byun D . Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses. Gastroenterology. 2007; 132(7):2459-77. DOI: 10.1053/j.gastro.2007.04.024. View