An interesting article today in Nature's Oncogene on Novogen's drug candidate phenoxodiol.
John had pointed to it on the NTII thread:
Message 18892191
Briefly, this is a genestein analog. (Genestein is likely the good stuff in soy beans).
Phenoxodiol - an isoflavone analog - induces apoptosis in chemoresistant ovarian cancer cells
Marijke Kamsteeg1, Thomas Rutherford1, Eva Sapi1, Bozena Hanczaruk1, Shoreh Shahabi1, Maryann Flick1, David Brown1,2 and Gil Mor1
1Department of Obstetrics and Gynecology, Yale University, School of Medicine, New Haven, CT, USA
Correspondence to: G Mor, Department of Obstetrics and Gynecology, Yale University, School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. E-mail: Gil.Mor@yale.edu
2Marshal Edwards, Inc North Ryde, Australia
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.
Oncogene (2003) 22, 2611-2620. doi:10.1038/sj.onc.1206422
At a quick glance the paper seems pretty solid - they showed an effect in a mouse model as well as the in vitro stuff described in their abstract. Their analog seems to be about 30X more potent than genestein in killing tumor cells.
Don't know anything at all about the company. Anyone ever look at them?
Peter |
