Camptothecin sensitizes androgen-independent prostate cancer cells to anti-Fas-induced apoptosis.

Abstract:

:Despite expressing both Fas and Fas ligand, DU145 and LNCaP prostate cancer cells were resistant to anti-Fas-induced cell death. Resistance to Fas-mediated cytotoxicity could be overcome in DU145, but not in LNCaP, cells by pretreating cells with sublethal doses of cytotoxic drugs, such as camptothecin. Activated caspases were shown to be required for this cytotoxicity. Indeed, poly(ADP-Ribose) polymerase was shown to be proteolytically cleaved in cells treated with camptothecin plus anti-Fas, but not in cells treated with anti-Fas only. Moreover, pretreatment of cells with ZVAD completely blocked camptothecin-mediated Fas-induced apoptosis. Sensitization of cells to Fas-induced cell death did not involve up-regulation of Fas or FasL, and it was independent of alterations in the cell cycle. Reactive oxygen intermediates (ROI) have been shown to be important mediators of drug-induced apoptosis. Here, we demonstrate that treatment of DU145 cells with camptothecin, anti-Fas, or both, did not alter the intracellular levels of peroxide or superoxide anion.

journal_name

Br J Cancer

authors

Costa-Pereira AP,Cotter TG

doi

10.1038/sj.bjc.6690365

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

371-8

issue

3-4

eissn

0007-0920

issn

1532-1827

journal_volume

80

pub_type

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