4.5 Article

Cribrostatin 6 induces death in cancer cells through a reactive oxygen species (ROS)-mediated mechanism

Journal

INVESTIGATIONAL NEW DRUGS
Volume 29, Issue 4, Pages 562-573

Publisher

SPRINGER
DOI: 10.1007/s10637-010-9390-x

Keywords

Cribrostatin 6; ROS; Quiescent 3T3; Quinone; HMOX1; Apoptosis; Cancer stem cells; Transcript profile; Quiescent cells; Drug-resistant cell lines

Funding

  1. University of Illinois

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Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell cycle arrest. Consistent with this data, we find that cribrostatin 6 treated cells have large amounts of reactive oxygen species (ROS) and, based on transcript profiling experiments and other data, this ROS generation is likely the primary mechanism by which cribrostatin 6 induces apoptosis. Given the success of certain ROS producers as anticancer agents, cribrostatin 6 has potential as a novel chemotherapeutic agent.

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