1. DNA damaging drugs-induced down-regulation of Bcl-2 is essential for induction of apoptosis in high-risk HPV-positive HEp-2 and KB cells
- Author
-
Rishi Raj Chhipa, Maleppillil Vavachan Vijayakumar, Manoj Kumar Bhat, and Sandeep Singh
- Subjects
Cancer Research ,Antimetabolites, Antineoplastic ,DNA damage ,Cell Survival ,Poly ADP ribose polymerase ,Down-Regulation ,Antineoplastic Agents ,Apoptosis ,Biology ,Poly(ADP-ribose) Polymerase Inhibitors ,Transfection ,Poly (ADP-Ribose) Polymerase Inhibitor ,KB Cells ,Carboplatin ,Cell Line, Tumor ,Humans ,RNA, Messenger ,Papillomaviridae ,Regulation of gene expression ,Dose-Response Relationship, Drug ,Papillomavirus Infections ,Molecular biology ,Caspase 9 ,Enzyme Activation ,Gene Expression Regulation, Neoplastic ,Oncology ,Proto-Oncogene Proteins c-bcl-2 ,Cell culture ,Caspases ,Cancer cell ,Cancer research ,Fluorouracil ,Poly(ADP-ribose) Polymerases - Abstract
DNA damaging chemotherapeutic agents like carboplatin (Carb) and 5-fluorouracil (5-FU), whose effects are mediated through diverse intracellular targets, induce apoptosis in various cancer cells including human papillomavirus (HPV) positive HEp-2 and KB cells. The present work reports the involvement of Bcl-2 in response to the exposure of HEp-2 and KB cells to Carb or 5-FU. We demonstrate that both these drugs are potent inducers of apoptosis. Apoptosis was preceded by decrease in Bcl-2 protein level accompanied by caspase-9 activation and poly(ADP-ribose) polymerase (PARP) cleavage without altering Bax expression. Further analysis revealed down-regulation of Bcl-2 mRNA as well as protein in drugs treated cells. Ectopic expression of Bcl-2 protected cells against drugs mediated DNA damage-induced apoptosis. Overall, data indicates that genotoxic stress leads to down-regulation of Bcl-2 in HEp-2 and KB cells, which plays a decisive role in the outcome of stress in these cells.
- Published
- 2005