Tamoxifen

Tamoxifen (TC), a selective estrogen receptor modulator (SERM), is used against breast cancer in both men and women. It also acts as a prophylactic agent against breast cancer in women. This protein kinase C inhibitor and anti-angiogenetic factor is a prodrug that is metabolized to active metabolites 4-hydroxytamoxifen (4-OHT) and endoxifen by cytochrome P450 isoforms CYP2D6 and CYP3A4. In breast cancer, the gene repressor activity of tamoxifen against ERBB2 is dependent upon PAX2. TC blocks estradiol-stimulated vascular endothelial growth factor (VEGF) production in breast tumor cells. Patients with estrogen receptor-positive tumors are more likely to benefit from tamoxifen. It exhibits both estrogenic agonist and antagonist effects by selectively binding to estrogen receptors in different parts of the body.

This nonsteroidal triphenylethylene derivative suppresses tumor growth and has been reported to be a carcinogen and teratogen in animals. Additionally, TC may also protect bone from estrogen-deficiency bone loss, lower plasma cholesterol, and have been implicated in liver carcinogenesis in rats. Other actions of TC include the reduction of plasma levels of insulin-like growth factor, induction of cells surrounding cancer cells to secrete transforming growth factor β, and inhibition of membrane lipid peroxidation, likely by decreasing membrane fluidity.

Tamoxifen has been used:

• in the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and crystal violet staining assay to access cell viability
• to induce Dicer ablation in Dicer-conditional mice, to study the effects of Dicer deficiency on adipocyte differentiation and function.
• to study its biological effects on the glucocorticoid (GC)-resistant cell line Jurkat, derived from acute lymphoblastic leukemia of T lineage (T-ALL)
• to study the physiological effects of tamoxifen treatment on the hypothalamus-POA mediated by estrogen receptor alpha (ERα) in mice
• to induce Cre recombinase activity for gene manipulation.
• to facilitate the recombination of the ect2^flox allele in mouse organs
• to study its effect on lipopolysaccharide (LPS)-induced microglial activation

Protein kinase C inhibitor. Induces apoptosis in human malignant glioma cell lines. Tamoxifen and its metabolite 4-hydroxytamoxifen are selective estrogen response modifiers (SERMs) that act as estrogen antagonists in mammary gland. Blocks estradiol-stimulated VEGF production in breast tumor cells.

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Tamoxifen is soluble in chloroform at 50 mg/ml and yields a clear, colorless to faint yellow solution. It is also soluble in methanol, ethanol, 2-propanol and propylene glycol. Stock solutions of tamoxifen can also be prepared in DMSO at 10 mM. However, it is practically insoluble in water (solubility is <0.01%, 20° C). Solutions are sensitive to UV light, and DMSO solutions are stable when stored at -20° C in the dark.