Tyrphostins and retinoids cooperate during inhibition of in vitro growth of ovarian cancer cells.

Signaling Networks Program, Clinical Division of Oncology, Department of Medicine I, University Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. thomas.grunt@akh-wien.ac.at

Cancer letters 2003 Jan 28

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Chemoresistance of ovarian cancer can be overcome by co-administration of retinoids, albeit clinical proof of this hypothesis is pending. Moreover, growth factor/c-erbB signaling is crucial for ovarian tumor growth/chemosensitivity. Retinoids and c-erbB modulators therefore represent promising drugs for ovarian cancer. We demonstrate that c-erbB-1 (RG-14620, AG1517) and c-erbB-2 selective tyrphostins (AG825, AG879), and all-trans and 9-cis retinoic acid inhibit ovarian cancer cell proliferation (HOC-7, OVCAR-3). Unlike retinoids, AG1517 and AG879 induce apoptosis. The antiproliferative activity of AG1517 is enhanced by all-trans retinoic acid suggesting that c-erbB and retinoid pathways interact. Thus, these agents cooperate during ovarian cancer cell growth inhibition.

Citation

Thomas W Grunt. Tyrphostins and retinoids cooperate during inhibition of in vitro growth of ovarian cancer cells. Cancer letters. 2003 Jan 28;189(2):147-56