کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10583815 981310 2014 18 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
New derivatives of lupane triterpenoids disturb breast cancer mitochondria and induce cell death
ترجمه فارسی عنوان
مشتقات جدید تریپرپوئید لوپان باعث اختلال در میتوکندری سرطان پستان می شود و باعث مرگ سلول می شود
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی
Novel cationic dimethylaminopyridine derivatives of pentacyclic triterpenes were previously described to promote mitochondrial depolarization and cell death in breast and melanoma cell lines. The objective of this work was to further investigate in detail the mechanism of mitochondrial perturbations, correlating those effects with breast cancer cell responses to those same agents. Initially, a panel of tumor and non-tumor cell lines was grown in high-glucose or glucose-free glutamine-containing media, the later forcing cells to synthesize ATP by oxidative phosphorylation only. Cell proliferation, cell cycle, cell death and mitochondrial membrane polarization were evaluated. Inhibition of cell proliferation was observed, accompanied by an arrest in the G1-cell cycle phase, and importantly, by loss of mitochondrial membrane potential. On a later time-point, caspase-9 and 3 activation were observed, resulting in cell death. For the majority of test compounds, we determined that cell toxicity was augmented in the galactose media. To investigate direct evidences on mitochondria isolated rat liver mitochondria were used. The results showed that the compounds were strong inducers of the permeability transition pore. Confirming our previous results, this work shows that the novel DMAP derivatives strongly interact with mitochondria, resulting in pro-apoptotic signaling and cell death.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 21, 1 November 2014, Pages 6270-6287
نویسندگان
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