Mechanisms of sulindac-induced apoptosis and cell cycle arrest.

Abstract:

:The mechanism underlying the chemopreventive effects of the non-steroidal anti-inflammatory drug sulindac remains unclear. Its active metabolite, sulindac sulfide, induces cell cycle arrest as well as apoptosis in mammalian cell lines. We now show that in murine thymocytes, sulindac sulfide-induced cell death is p53, bax, Fas, and FasL independent. In contrast, bcl2 transgenic thymocytes are resistant to sulindac sulfide-induced apoptosis. In addition, we demonstrate that sulindac sulfide-induced cell cycle arrest in mouse embryonic fibroblasts (MEFs) is partly mediated by the retinoblastoma tumor suppressor protein (Rb) and the cyclin kinase inhibitor p21waf1/cip1. Furthermore, MEFs deficient in p21 or Rb are more susceptible to sulindac sulfide-induced cell death. These results suggest that sulindac may selectively target premalignant cells with cell cycle checkpoint deficits.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Jung B,Barbier V,Brickner H,Welsh J,Fotedar A,McClelland M

doi

10.1016/j.canlet.2004.06.015

keywords:

subject

Has Abstract

pub_date

2005-02-28 00:00:00

pages

15-25

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(04)00460-4

journal_volume

219

pub_type

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