title: The anti-proliferative effects of tyrosine kinase inhibitors towards tamoxifen-sensitive and tamoxifen-resistant human breast cancer cell lines in relation to the expression of epidermal growth factor receptors (EGF-R) and the inhibition of EGF-R tyrosine kinase.
abstract: We have investigated the anti-proliferative effect of the tyrosine kinase inhibitors genistein, lavendustin A and 2,5-dihydromethylcinnimate (2,5-MeC) (a stable erbstatin analogue) against the epidermoid A431 cell line, the ZR-75-1 human breast cancer cell line and tamoxifen-resistant (ZR-75-9a1) and oestrogen-independent (ZR-PR-LT) variants. Increased EGF-R expression by ZR-75-9a1 was associated with decreased sensitivity to genistein and 2,5-MeC whilst decreased EGF-R expression (ZR-PR-LT) cells was associated with increased sensitivity to lavendustin A and 2,5-MeC. Anti-proliferative IC50 concentrations of 2,5-MeC, but not genistein or lavendustin A, inhibited EGFR-R associated tyrosine kinase activity of ZR-75-1 cells and variants by 20-50%.
authors.affiliation: Department of Oncology, The Queen's University of Belfast, Belfast City Hospital, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: El-Zarruk
authors.forename: H W
authors.initials: HW
authors.lastname: van den Berg
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D010636:Phenols / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; D004791:Enzyme Inhibitors; D010636:Phenols; D013629:Tamoxifen; C062898:lavendustin A; C087931:ethyl 2,5-dihydroxycinnamate; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases