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

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.

• Authors: Mirth T Hoyt, Rahul Palchaudhuri, Paul J Hergenrother
• Journal: Investigational new drugs (Invest New Drugs) Vol. 29 Issue 4 Pg. 562-73 (Aug 2011) ISSN: 1573-0646 [Electronic] United States
• PMID: 20169400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoquinolines
• RNA, Messenger
• Reactive Oxygen Species
• cribrostatin 6
• DNA
• HMOX1 protein, human
• Heme Oxygenase-1
• DNA Topoisomerases, Type I
• DNA Topoisomerases, Type II
• Ethidium
• Acetylcysteine
• Camptothecin

Topics

• 3T3 Cells
• Acetylcysteine (pharmacology)
• Animals
• Camptothecin (pharmacology)
• Cell Cycle (drug effects)
• Cell Death (drug effects)
• Cell Hypoxia (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytoprotection (drug effects)
• DNA (metabolism)
• DNA Topoisomerases, Type I (metabolism)
• DNA Topoisomerases, Type II (metabolism)
• Down-Regulation (drug effects)
• Drug Screening Assays, Antitumor
• Ethidium (metabolism)
• Fibroblasts (cytology, drug effects)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Heme Oxygenase-1 (genetics, metabolism)
• Humans
• Isoquinolines (chemical synthesis, chemistry, pharmacology)
• Mice
• RNA, Messenger (genetics, metabolism)
• Reactive Oxygen Species (metabolism)
• Up-Regulation (drug effects)