Tyrphostins and retinoids cooperate during inhibition of in vitro growth of ovarian cancer cells.
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.
Grunt
Thomas W
TW
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
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles; D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology*; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D020032:Tyrphostins / Q000494:pharmacology*
D052160:Benzothiazoles; D066246:ErbB Receptors; D009363:Neoplasm Proteins; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014212:Tretinoin; D020032:Tyrphostins; C108081:AG 1517; C081020:AG-879; C098214:tyrphostin AG825; C070273:RG 14620