Tamoxifen Citrate

Tamoxifen Citrate displays antitumor effect due to its antiestrogenic activity (ER). Values for the apparent affinity of this compound for the ER range between 30 and 0.01% of that obtained for estradiol, dependent on different ER source (species), protein concentration and condition used for assay. Binding of this chemical to ER further leads to inhibition expression of estrogen-regulated genes, including growth factors and angiogenic factors secreted by the tumor that may stimulate growth by autocrine or paracrine mechanisms. It also directly induces programmed cell death. [1] This compound produces an inhibitory effect on MCF-7 cell [³H]thymidine incorporation and DNA polymerase activity as well as causing a reduction in DNA content of cultures and cell numbers. This inhibitory effect of this chemical on MCF-7 cell growth can be readily reversed by addition of estradiol to the culture medium. 2 and 6 μM of this agent reduces the proportion of cells in S phase and increases the number of cells in G1. At 10 μM, it causes cell death within 48 hr. [2] This compound inhibits MCF-7 growth with IC50 of ~10 nM after 10 days treatment. It inhibits plasminogen activator activity of MCF-7, and suppresses estradiol-stimulation of plasminogen activator activity. This chemical also evokes minimal increases in cellular progesterone receptor levels. [3] It is able to inhibit the growth of prostate cancer cell PC3, PC3-M, and DU145 with IC50 ranged from 5.5-10 μM, which is related to its inhibition of protein kinase C and induction of p21(waf1/cip1). [4]

Tamoxifen Citrate administration to rapidly growing, estradiol-stimulated MCF-7 xenografts results in a dose-dependent retardation or cessation of tumor growth by significantly decreasing tumor cell proliferation in tumor. This compound treatment results in a slowing of tumor growth (tumor doubling time, 12 days), a significant increase in tumor potential doubling time (T_pot) (6.6 days), and a decrease in labeling index (%LI) (to 8%) by 23 days posttreatment, compared with untreated mice which shows a volume doubling time of 5 days, a T_pot of 2.3 days, and a %LI of 23%. [5] It has not only antiestrogenic but also estrogenic properties depending on the species, tissue, and gene. This chemical displays favorable effects on bone and serum lipid concentrations and stimulation endometrium. [1]

MCF-7 cells are seeded into T-25 flasks (1.5×10⁵ cells/flask) and grown for 2 days in the MEM supplemented with 10 mM HEPES buffer, gentamicin (50 μg/mL), penicillin (100 units/mL), streptomycin (0.1 mg/mL), bovine insulin (6 ng/mL), hydrocortisone (3.75 ng/mL), and 5% calf serum that has been treated with dextran-coated charcoal for 45 min at 55 ℃ to remove endogenous hormones. The medium is then changed to MEM supplemented as described above, except that it contains 2% charcoal dextran-treated calf serum and various concentrations of this compound. At the end of incubation, cell numbers are counted.

• https://pubmed.ncbi.nlm.nih.gov/9828250/
• https://pubmed.ncbi.nlm.nih.gov/6438654/
• https://pubmed.ncbi.nlm.nih.gov/6537799/

• https://pubmed.ncbi.nlm.nih.gov/9721069/
• https://pubmed.ncbi.nlm.nih.gov/8364937/
• https://pubmed.ncbi.nlm.nih.gov/10963646/

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