Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim

R. Li, T. Moudgil, H. J. Ross, H. M. Hu

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

A significant variation in susceptibility to paclitaxel-mediated killing was observed among a panel of short-term cultured non-small-cell lung cancer (NSCLC) cell lines. Susceptibility to killing by paclitaxel correlated with expression of the BH3-only protein, Bim, but not with other members of Bcl-2 family. NSCLC cell lines with the highest level of Bim expression are most susceptible to apoptosis induction after paclitaxel treatment. Forced expression of Bim increased paclitaxel-mediated killing of cells expressing an undetectable level of Bim. Conversely, knock down of Bim, but not Bcl-2 expression, decreased the susceptibility of tumor cells to paclitaxel-mediated killing. Similar observations were made using a panel of breast and prostate cancer cell lines. Paclitaxel impairs microtubule function, causes G2/M cell cycle blockade, mitochondria damage, and p53-independent apoptosis. These results established Bim as a critical molecular link between the microtubule poison, paclitaxel, and apoptosis.

Original languageEnglish (US)
Pages (from-to)292-303
Number of pages12
JournalCell Death and Differentiation
Volume12
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Bim
  • Non-small-cell lung cancer
  • Paclitaxel

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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