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

Mirth T. Hoyt, Rahul Palchaudhuri, Paul J. Hergenrother

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)562-573
Number of pages12
JournalInvestigational New Drugs
Volume29
Issue number4
DOIs
StatePublished - Aug 1 2011

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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