Biochemical mechanism of cross-resistance to paclitaxel in a mitomycin c-resistant human bladder cancer cell line

Richard J. Bleicher, Hong Xia, Howard A. Zaren, Shivendra V. Singh

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The present study describes the biochemical mechanism(s) of cross- resistance to paclitaxel in a human bladder cancer cell line (J82/MMC-2), which is >9-fold more resistant to mitomycin C (MMC) than parental cells (J82/WT). The IC50 values for paclitaxel in J82/WT and J82/MMC-2 cell lines were 0.7 ± 0.03 and 2.8 ± 0.7 μM, respectively (P < 0.05). Thus, the J82/MMC-2 cell line exhibited 4-fold cross-resistance to paclitaxel compared with J82/WT. Intracellular accumulation of [3H]paclitaxel was comparable in J82/WT and J82/MMC-2 cell lines. There were no qualitative or quantitative differences between the J82/WT and J82/MMC-2 cell lines in terms of their α- tubulin and β-tubulin contents. Paclitaxel-induced apoptosis could not be detected in either cell line over a wide range of drug concentrations. These results indicate that cross-resistance to paclitaxel in the J82/MMC-2 cell line is not linked to reduced drug accumulation, increased drug efflux, alterations in tubulin content or reduced paclitaxel-induced apoptosis. Paclitaxel-induced DNA strand breakage, however, determined by alkaline elution, was markedly lower in the J82/MMC-2 cell line than in J82/WT. These results suggest that paclitaxel cross-resistance in J82/MMC-2 may be attributed to reduced paclitaxel-induced DNA strand breakage. The precise mechanism of reduced paclitaxel-induced DNA strand breakage in J82/MMC-2 cell line relative to J82/WT cells, however, remains to be elucidated. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalCancer Letters
Volume150
Issue number2
DOIs
StatePublished - Mar 31 2000

Keywords

  • Bladder cancer
  • DNA damage
  • Drug resistance
  • Mitomycin C
  • Paclitaxel
  • Taxol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Biochemical mechanism of cross-resistance to paclitaxel in a mitomycin c-resistant human bladder cancer cell line'. Together they form a unique fingerprint.

Cite this