Effects of (5z)-7-Oxozeaenol on the Oxidative Pathway of Cancer Cells

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Cedric J Pearce, Adjunct Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: Aim: As part of an on going investigation of novel anticancer agents from natural origin, the biological and cellular effects of (5Z)-7-oxozeaenol on cancer cells were investigated. Materials and Methods: The expression of nuclear factor kappa B (NF-?B), I?B kinase (IKKa), IKKß and caspase-3 were analyzed by western blot. Reactive oxygen species (ROS) fluorescence and caspase luminescent assays were used to assess the intracellular effects in HeLa cervical and HT-29 colon cancer cell lines. The mitochondrial transmembrane potential (MTP) was analyzed by fluorescence-activated cell sorting (FACS). Results: Cells treated with (5Z)-7-oxozeaenol exhibited down-regulation of NF-?B in a dose-dependent manner. Treatment with (5Z)-7-oxozeaenol significantly enhanced the levels of ROS in HeLa and HT-29 cells. MTP was reduced in HT-29 cells. The expression of caspase-3 and -7 was induced in (5Z)-7-oxozeaenol treated HeLa cells, in comparison with those treated with paclitaxel. Conclusion: Our findings suggest that (5Z)-7-oxozeaenol is a potent inhibitor of the NF-?B pathway and potentiates the production of ROS, as well as induces caspase-3 and -7 in HeLa and HT-29 cancer cells. Thus, (5Z)-7-oxozeaenol represents a new lead compound for drug development, particularly as a new cancer chemotherapeutic agent, since programmed cell death might be mediated through the activation of a caspase-arbitrated pathway.

Additional Information

Anticancer Research, 32 (7), 2665-2671
Language: English
Date: 2012
(5Z)-7-Oxozeaenol, NF-?B pathway, apoptosis, caspase, IKKa, IKKß, ROS, HeLa, HT-29 cells

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