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

被引：16

作者：

Singh, Sandeep ^{[1
]}

Chhipa, Rishi Raj ^{[1
]}

Vijayakumar, Maleppillil Vavachan ^{[1
]}

Bhat, Manoj Kumar ^{[1
]}

机构：

[1] Natl Ctr Cell Sci, Pune 411007, Maharashtra, India

来源：

CANCER LETTERS | 2006年 / 236卷 / 02期

关键词：

HPV-positive carcinoma; DNA damage; Bcl-2; promoter; apoptosis;

D O I：

10.1016/j.canlet.2005.05.024

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

引用

页码：213 / 221

页数：9

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