The Sound of Evolution
Tamoxifen
Mechanism of action:
Tamoxifen is a selective estrogen receptor modulator. Tamoxifen binds to estrogen receptors ERa and ERb, preventing endogenous estradiol from binding to them. In breast cancer cells, the tamoxifen-estrogen receptor complex cannot efficiently recruit coactivators and instead tends to recruit corepressors, thereby suppressing estrogen-dependent gene transcription, inhibiting breast cancer cell proliferation, and promoting apoptosis.
Reference(s):
1. Jordan VC et al. (1993). Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol.
2. Howell A et al. (2005). Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet.
3. Crewe HK et al. (2002). Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos.