کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8322495 | 1539875 | 2015 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Exemestane metabolites suppress growth of estrogen receptor-positive breast cancer cells by inducing apoptosis and autophagy: A comparative study with Exemestane
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کلمات کلیدی
Phosphatidylinositol 3-KinasesCCCP3-MADCFH2-DAphorbol 12-myristate 13-acetateΔΨmAISRLUExemestaneSTSCyP7-AADMFI7-amino-actinomycin DFBSDMEMCFBsPI3KAVOs2′,7′-dichlorodihydrofluorescein diacetate - 2 '، 7'-dichlorodihydrofluorescein diacetate3-methyladenine - 3-متیل آدنینDiOC6(3) - DiOC6 (3)ER+ - ER +PMA - LDC هاDulbecco's modified Eagle's medium - Medal of Eagle اصلاح شده DulbeccoMTT - MTTROS - ROScytochrome P450 enzymes - آنزیم های سیتوکروم P450Acridine orange - آکاردین نارنجیAutophagy - اتوفاژیstaurosporine - استوسوسورپینtestosterone - تستوسترونApoptosis - خزان یاختهایfetal bovine serum - سرم جنین گاوPhosphatidylserine - فسفاتیدیلسرینMEM - مامانEstrogen receptor-positive - مثبت گیرنده استروژنAromatase inhibitors - مهار کننده های آراماتازmean fluorescence intensity - میانگین شدت فلورسانسrelative luminescence units - واحد لومینسانس نسبیMitochondrial transmembrane potential - پتانسیل ترانزیتی میتوکندریPropidium iodide - پروتئین یدیدcarbonyl cyanide m-chlorophenylhydrazone - کربنیل سیانید m-chlorophenylhydrazoneintracellular reactive oxygen species - گونه های اکسیژن واکنشی داخل سلولیEstrogen receptor - گیرنده استروژن3,3′-dihexyloxacarbocyanine iodide - یدید 3،3'-dihexyloxacarbocyanine
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Around 60-80% of all breast tumors are estrogen receptor-positive. One of the several therapeutic approaches used for this type of cancers is the use of aromatase inhibitors. Exemestane is a third-generation steroidal aromatase inhibitor that undergoes a complex and extensive metabolism, being catalytically converted into chemically active metabolites. Recently, our group showed that the major exemestane metabolites, 17β-hydroxy-6-methylenandrosta-1,4-dien-3-one and 6-(hydroxymethyl)androsta-1,4,6-triene-3,17-dione, as well as, the intermediary metabolite 6β-Spirooxiranandrosta-1,4-diene-3,17-dione, are potent aromatase inhibitors in breast cancer cells. In this work, in order to better understand the biological mechanisms of exemestane in breast cancer and the effectiveness of its metabolites, it was investigated their effects in sensitive and acquired-resistant estrogen receptor-positive breast cancer cells. Our results indicate that metabolites induced, in sensitive breast cancer cells, cell cycle arrest and apoptosis via mitochondrial pathway, involving caspase-8 activation. Moreover, metabolites also induced autophagy as a promoter mechanism of apoptosis. In addition, it was demonstrated that metabolites can sensitize aromatase inhibitors-resistant cancer cells, by inducing apoptosis. Therefore, this study indicates that exemestane after metabolization originates active metabolites that suppress the growth of sensitive and resistant breast cancer cells. It was also concluded that, in both cell lines, the biological effects of metabolites are different from the ones of exemestane, which suggests that exemestane efficacy in breast cancer treatment may also be dependent on its metabolites.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 69, December 2015, Pages 183-195
Journal: The International Journal of Biochemistry & Cell Biology - Volume 69, December 2015, Pages 183-195
نویسندگان
Cristina Amaral, Andreia Lopes, Carla L. Varela, Elisiário Tavares da Silva, Fernanda M.F. Roleira, Georgina Correia-da-Silva, Natércia Teixeira,