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

Abstract

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.

• Authors: Thomas W Grunt
• Journal: Cancer letters (Cancer Lett) Vol. 189 Issue 2 Pg. 147-56 (Jan 28 2003) ISSN: 0304-3835 [Print] Ireland
• PMID: 12490307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AG 1517
• AG-879
• Benzothiazoles
• Neoplasm Proteins
• Quinazolines
• Tyrphostins
• tyrphostin AG825
• RG 14620
• Tretinoin
• ErbB Receptors
• Receptor, ErbB-2

Topics

• Adenocarcinoma (enzymology, pathology)
• Apoptosis (drug effects)
• Benzothiazoles
• Cell Division (drug effects)
• Drug Resistance, Neoplasm
• Drug Synergism
• ErbB Receptors (antagonists & inhibitors)
• Female
• Humans
• Neoplasm Proteins (antagonists & inhibitors)
• Ovarian Neoplasms (enzymology, pathology)
• Quinazolines (pharmacology)
• Receptor, ErbB-2 (antagonists & inhibitors)
• Tretinoin (pharmacology)
• Tumor Cells, Cultured (cytology, drug effects, enzymology)
• Tyrphostins (pharmacology)