Investigational New Drugs

, Volume 29, Issue 4, pp 562–573

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

  • Mirth T. Hoyt
  • Rahul Palchaudhuri
  • Paul J. Hergenrother
PRECLINICAL STUDIES

Summary

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.

Keywords

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

Supplementary material

10637_2010_9390_MOESM1_ESM.pdf (2 mb)
Supporting Information AvailableMaterials and methods, spectral data for all new compounds, and pathway diagrams based on transcript profiling experiments. (PDF 2083 kb)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mirth T. Hoyt
    • 1
  • Rahul Palchaudhuri
    • 1
  • Paul J. Hergenrother
    • 1
  1. 1.Department of Chemistry, Roger Adams LaboratoryUniversity of IllinoisUrbanaUSA

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