Induction of apoptosis by cryptophycin 1, a new antimicrotubule agent

Susan L. Mooberry, Lizette Busquets, Georgia Tien

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

The ability of cryptophycin I, a new potent cytotoxic antimicrotubule agent, to initiate apoptosis was studied. Treatment of cells with cryptophycin I (50 pM) rapidly caused morphological changes consistent with the induction of apoptosis. DNA strand breakage and fragmentation of the DNA into oligonucleosome-sized fragments was observed, and this coincided with the loss of cellular DNA. Activation of the cysteine protease CPP32 (caspase 3, YAMA, apopain), a member of the ICE/CED-3-like protease family of apoptosis effectors, was consistent with the execution of cell death by a coordinated sequence of events. Low concentrations of cryptophycin I caused mitotic arrest with the formation of abnormal mitotic spindles without affecting interphase microtubule structures. Unlike other microtubule active agents, cryptophycin-induced mitotic arrest persisted for only a brief period before the onset of apoptosis. There was no evidence of release from G2/M cell cycle arrest. Our results show that low concentrations of cryptophycin I (50 pM) initiated cell death consistent with apoptosis. These data suggest that the cytotoxic effects of cryptophycin I are due in part to its ability to initiate apoptosis rapidly.

Original languageEnglish (US)
Pages (from-to)440-448
Number of pages9
JournalInternational Journal of Cancer
Volume73
Issue number3
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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