By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Investigators publish new report on Biotechnology. According to news reporting originating from Little Rock, Arkansas, by NewsRx correspondents, research stated, "Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells."
Our news editors obtained a quote from the research from the University of Arkansas, "These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9-3 mu M). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs."
According to the news editors, the research concluded: "Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel, efficacious, non-toxic cancer drugs acting via CB1 and/or CB2Rs."
For more information on this research see: CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen. Biochemical and Biophysical Research Communications, 2013;441(2):339-343. Biochemical and Biophysical Research Communications can be contacted at: Academic Press Inc Elsevier Science, 525 B St, Ste 1900, San Diego, CA 92101-4495, USA. (Elsevier - www.elsevier.com; Biochemical and Biophysical Research Communications - www.elsevier.com/wps/product/cws_home/622790)
The news editors report that additional information may be obtained by contacting P.L. Prather, University of Arkansas, Dept. of Biochem & Mol Biol, Coll Med, Little Rock, AR 72205, United States. Additional authors for this research include F. FrancisDevaraj, C.R. Dates, A.K. Greer, S.M. Bratton, B.M. Ford, L.N. Franks and A. Radominska-Pandya (see also Biotechnology).
Keywords for this news article include: Biotechnology, Drugs, Arkansas, Oncology, Stilbenes, Tamoxifen, Little Rock, United States, Breast Cancer, Women's Health, Benzene Derivatives, Cancer Gene Therapy, North and Central America, Hormones - Antineoplastics, Selective Estrogen Receptor Modulators
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