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

Cancer Lett. 2003 Jan 28;189(2):147-56. doi: 10.1016/s0304-3835(02)00512-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / 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
  • Ovarian Neoplasms / pathology*
  • Quinazolines / pharmacology*
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Tyrphostins / pharmacology*

Substances

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