کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10757204 | 1050393 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
IBMXDulbecco’s Modification of Eagle’s MediumWIN-55,212-2HMoRCP-55,940SERMCB2RCB1RGPCRDMEMG-protein coupled receptor - G-پروتئین همراه گیرندهG-protein coupled receptors - G-پروتئین گیرنده های متصل شده[35S]GTPγS - [35S] GTPγSadenylyl cyclase - آدنیلات سیکلاز، آدنیلیل سیکلازAntagonist - آنتاگونیستInverse agonist - آگونیست معکوسDrug action - اقدامات داروییCho - برایTAM - تامtamoxifen - تاموکسیفنChinese Hamster Ovary - تخمدان هامستر چینیSelective estrogen receptor modulator - مدولاتور گیرنده استروژن انتخابیcannabinoid receptor type 1 - نوع گیرنده کانابینوئید 1Cannabinoids - کانابینوئیدDrug discovery - کشف مواد مخدرEstrogen receptor - گیرنده استروژنcannabinoid receptors - گیرنده های کانابینوئیدcannabinoid receptor type 2 - گیرنده کانابینوئید نوع 2
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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. 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 μM). 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. 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 441, Issue 2, 15 November 2013, Pages 339-343
Journal: Biochemical and Biophysical Research Communications - Volume 441, Issue 2, 15 November 2013, Pages 339-343
نویسندگان
Paul L. Prather, FeAna FrancisDevaraj, Centdrika R. Dates, Aleksandra K. Greer, Stacie M. Bratton, Benjamin M. Ford, Lirit N. Franks, Anna Radominska-Pandya,