The cytotoxic effect of tamoxifen (TAM) was investigated in the T-289 melanoma cell line, as well as the 289 DDP3 cisplatin (DDP)-resistant and the 289 TAM6 TAM-resistant variant melanoma cell lines to determine the effect of drug resistance on synergy. T-289 melanoma cells were made DDP or TAM resistant through chronic exposure to increasing concentrations of the respective drugs. Whereas DDP ...

The triphenylethylene antiestrogen tamoxifen (TAM) is believed to exert its antitumor effect via the estrogen receptor (ER). To test this hypothesis and to differentiate between ER-mediated and general cytotoxic effects of TAM, the growth-inhibitory effects of TAM and its in vivo metabolite 4-hydroxytamoxifen (OH-TAM) have been studied in five continuous human cancer cell lines, MCF7 and T47D (...

Tamoxifen (tam), an anti-breast cancer agent, is metabolized into tam-N-oxide by the hepatic flavin-containing monooxygenase and into N-desmethyl- and 4-hydroxy-tam by cytochrome P-450s (CYPs). Additionally, tam is metabolically activated by hepatic CYP3A, forming a reactive intermediate that binds covalently to proteins. Tam and 4-hydroxyandrostenedione (4-OH-A) are currently used to treat bre...

Tamoxifen (TAM) is used as the standard endocrine therapy for breast cancer patients and as a chemopreventive agent for women at high risk for this disease. Unfortunately, treatment of TAM increases the incidence of endometrial cancer; this may be due to the genotoxic damage induced by TAM metabolites. Formation of TAM-DNA adducts in rat liver correlates with the development of hepatocarcinoma....

Tamoxifen (TAM) is successfully used for the treatment and prevention of breast cancer. However, many patients that are initially TAM responsive develop tumors that are antiestrogen/TAM resistant (TAM-R). The mechanism behind TAM resistance in estrogen receptor alpha (ERalpha)-positive tumors is not understood. The orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor...