4.6 Article

5-Aza-2'-deoxycytidine stress response and apoptosis in prostate cancer

Journal

CLINICAL EPIGENETICS
Volume 2, Issue -, Pages 339-348

Publisher

BIOMED CENTRAL LTD
DOI: 10.1007/s13148-010-0019-x

Keywords

Epigenome; CpG hypermethylation; DNMT; 5-Aza-2 '-deoxycytidine; Apoptosis; Prostate cancer

Funding

  1. National Institute of Health [DK47517, AG-16870, CA64872]
  2. Veterans Affairs Medical Center
  3. NCIRE

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While studying on epigenetic regulatory mechanisms (DNA methylation at C-5 of -CpG- cytosine and demethylation of methylated DNA) of certain genes (FAS, CLU, E-cadh, CD44, and Cav-1) associated with prostate cancer development and its better management, we noticed that the used in vivo dose of 5-aza-2'-deoxycytidine (5.0 to 10.0 nM, sufficient to inhibit DNA methyltransferase activity in vitro) helped in the transcription of various genes with known (steroid receptors, AR and ER; ER variants, CD44, CDH1, BRCA1, TGF beta R1, MMP3, MMP9, and UPA) and unknown (DAZ and Y-chromosome specific) proteins and the respective cells remained healthy in culture. At a moderate dose (20 to 200 nM) of the inhibitor, cells remain growth arrested. Upon subsequent challenge with increased dose (0.5 to 5.0 mu M) of the inhibitor, we observed that the cellular morphology was changing and led to death of the cells with progress of time. Analyses of DNA and anti-, pro-, and apoptotic factors of the affected cells revealed that the molecular events that went on are characteristics of programmed cell death (apoptosis).

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