Arsenic trioxide and paclitaxel induce apoptosis by different mechanisms

Cagla Akay, Charles Thomas, Yair Gazitt

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Arsenic trioxide (ATO) and paclitaxel (TAXOL) are effective in the treatment of various types of cancers. Both drugs induce G2/M arrest. We have previously shown that ATO is a potent inducer of apoptosis in myeloma cells expressing mutant p53 engaging both the intrinsic and extrinsic apoptotic pathways. Here we compared the effect of ATO and TAXOL on myeloma cells expressing mutant p53 and varying levels of Bcl-2. ATO rapidly induced Apo2/TRAIL, activation of caspase 8, cleavage of BID, depolarization of mitochondrial membrane (MM) and release of AIF from mitochondria in a Bcl-2 independent fashion. Apoptosis was associated with early formation of ring-like perinuclear condensed chromatin colocalized with AIF. In contrast, paclitaxel-induced apoptosis MM depolarization, cytochrome C release and activation of caspase 9 were all blocked by Bcl-2. Apoptosis was associated with a random chromatin condensation and nuclear fragmentation with no early involvement of AIF.

Original languageEnglish (US)
Pages (from-to)324-334
Number of pages11
JournalCell Cycle
Volume3
Issue number3
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • AIF
  • Apoptosis
  • Arsenic trioxide
  • Cell cycle
  • Myeloma
  • Taxol

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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