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

Authors

  • Mirth T. Hoyt
    • Department of Chemistry, Roger Adams LaboratoryUniversity of Illinois
  • Rahul Palchaudhuri
    • Department of Chemistry, Roger Adams LaboratoryUniversity of Illinois
    • Department of Chemistry, Roger Adams LaboratoryUniversity of Illinois
PRECLINICAL STUDIES

DOI: 10.1007/s10637-010-9390-x

Cite this article as:
Hoyt, M.T., Palchaudhuri, R. & Hergenrother, P.J. Invest New Drugs (2011) 29: 562. doi:10.1007/s10637-010-9390-x

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 6ROSQuiescent 3T3QuinoneHMOX1ApoptosisCancer stem cellsTranscript profileQuiescent cellsDrug-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)

Copyright information

© Springer Science+Business Media, LLC 2010