Phenoxodiol--an isoflavone analog--induces apoptosis in chemoresistant ovarian cancer cells.

Abstract	Interference with the innate apoptotic activity is a hallmark of neoplastic transformation and tumor formation. In this study we characterize the cytotoxic effect of phenoxodiol, a synthetic anticancer drug analog of genestein, and demonstrate the mechanism of action by which phenoxodiol affects the components of the Fas apoptotic pathway on ovarian cancer cells. Primary ovarian cancer cells, isolated from ascitic fluids of ovarian cancer patients, resistant to conventional chemotherapy, undergo apoptosis following phenoxodiol treatment. This effect is dependent upon the activation of the caspase system, inhibiting XIAP, an inhibitor of apoptosis, and disrupting FLICE inhibitory protein (FLIP) expression through the Akt signal transduction pathway. We suggest that phenoxodiol is an efficient inducer of cell death in ovarian cancer cells and sensitizes the cancer cells to Fas-mediated apoptosis. We identified FLIP and XIAP signalling pathways as key factors regulating the survival of ovarian cancer cells. These findings demonstrate a novel nontoxic drug that controls FLIP/XIAP function and has the potential to eliminate tumor cells through Fas-mediated apoptosis.
Authors	Marijke Kamsteeg, Thomas Rutherford, Eva Sapi, Bozena Hanczaruk, Shoreh Shahabi, Maryann Flick, David Brown, Gil Mor
Journal	Oncogene (Oncogene) Vol. 22 Issue 17 Pg. 2611-20 (May 01 2003) ISSN: 0950-9232 [Print] England
PMID	12730675 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antineoplastic Agents Benzopyrans CASP8 and FADD-Like Apoptosis Regulating Protein CFLAR protein, human Carrier Proteins FASLG protein, human Fas Ligand Protein Intracellular Signaling Peptides and Proteins Isoflavones Membrane Glycoproteins Phenols Proteins X-Linked Inhibitor of Apoptosis Protein XIAP protein, human fas Receptor phenoxodiol CASP8 protein, human CASP9 protein, human Caspase 8 Caspase 9 Caspases
Topics	Antineoplastic Agents (pharmacology) Apoptosis (drug effects) Benzopyrans (pharmacology) CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins (antagonists & inhibitors) Caspase 8 Caspase 9 Caspases (physiology) Cell Line Drug Resistance, Neoplasm Fas Ligand Protein Female Humans Intracellular Signaling Peptides and Proteins Isoflavones (chemistry) Membrane Glycoproteins (metabolism) Ovarian Neoplasms (drug therapy) Phenols (pharmacology) Proteins (antagonists & inhibitors) Signal Transduction (physiology) X-Linked Inhibitor of Apoptosis Protein fas Receptor (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!