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Urol Res. 2002 Oct;30(5):282-8. Epub 2002 Sep 19.

Involvement of mitochondrial pathway in Taxol-induced apoptosis of human T24 bladder cancer cells.

Author information

1
Department of Surgery, Taichung Veterans General Hospital, No 160, section 3, Chung-Gang Road, Taichung, Taiwan.

Abstract

We examined a human urothelial cancer T24 cell line, which was exposed to clinically achievable concentrations of Taxol and detected the lethal effect of Taxol as measured by a cytotoxic dose-response curve. Marked nuclear condensation and the fragmentation of chromatin were observed by DAPI stain, DNA ladder formation, and flow cytometry at an LC(90)concentration of 0.8 microg/ml Taxol, which also induced a G2/M arrest. In response to Taxol-treatment, caspase-9 activity increased at 8 h, and both caspase-2 and -3 activities were increased twofold relative to control cultures at 16 h. Moreover, treatment with the broad-spectrum caspase inhibitor (z-VAD-fmk) or the caspase-9 specific inhibitor (z-LEHD-fmk) effectively protected T24 cells against Taxol-triggered apoptosis. Furthermore, the phosphorylation of Bcl-2 and Bcl-X(L) proteins in Taxol treated cells was detected at 8 h. In contrast, Taxol had no effect on the levels of Fas and FasL proteins and neither antagonistic, anti-Fas antibody affected Taxol-induced apoptosis. These results suggest that, following the phosphorylation of Bcl-2 and Bcl-X(L)proteins, Taxol-induced apoptosis is induced through the mitochondria-dependent pathway in T24 cells.

PMID:
12389115
DOI:
10.1007/s00240-002-0263-4
[Indexed for MEDLINE]

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