Tamoxifen

Parabens are a group of preservatives that have vast indications in pharmaceuticals, cosmetics and food industries. Recently, there have been reports about the estrogenic effects of these compounds which raised concerns about the possibility of involvement of parabens in estrogen-responsive cancers. In the current study, the effect of methylparaben (MP) and propylparaben (PP) was assessed on the growth pattern of human breast adenocarcinoma cell line, MCF-7. 17-ß-estradiol (EST) and tamoxifen (TAM) were used as estrogenic and anti-estrogenic compounds. EC50 of EST and IC50 of TAM were calculated to be 1.206 and 7.017 µg/ml, respectively, based on trypan blue dye exclusion assay in a 5-day exposure. Proliferation kinetics of MCF-7 cells in a 10 day exposure to these compounds showed that EST (1.206 µg/ml) could induce cell proliferation, while exposure of MP or PP (at the same dose) did not change the growth curve of MCF-7. TAM, on the other hand could decrease the proliferation rate of MCF-7. This inhibition was more exacerbated when MP and PP were added to the culture media, suggesting a competitive binding of these compounds to receptors. In conclusion, the data propose the probable estrogenic effect of MP and PP with less potency compared to EST and less competitive binding to ERs compared to TAM.

Mitochondrion plays an important role in cellular metabolism and in energy production. Free radicals contribute damage to mitochondria during various pathological conditions. Tamoxifen is an anti-estrogen drug given to treat breast cancer. Tamoxifen and its metabolites induce varied cellular effects. It was therefore planned to study the impact of tamoxifen on mitochondria to observe its mechanism of action in promoting cell death. Mitochondrion was isolated from sheep liver and different concentrations of tamoxifen were added to study its impact on oxidative stress. Tamoxifen induced swelling of mitochondria which in turn produced lipid peroxides in a dose-dependent manner. Tamoxifen significantly increased the levels of nitrite and nitrate in mitochondria with depletion of glutathione. It was observed that tamoxifen increased NADH oxidation leading to the release of calcium from mitochondria. These changes observed are correlated with the mechanism of action of tamoxifen in treating breast cancer.