کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8949695 | 1645722 | 2018 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
SAHA and cisplatin sensitize gastric cancer cells to doxorubicin by induction of DNA damage, apoptosis and perturbation of AMPK-mTOR signalling
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کلمات کلیدی
AMPKTSAmTORNHEJHDACHDACiSAHAH3K36Suberoylanilide hydroxamic acid - اسید سدئروانیلید هیدروکسامTrichostatin A - تریکوستاتین Anon-homologous end joining - عدم پیوستن انتهای غیر همولوگhistone deacetylase inhibitor - مهار کننده هیستون داسیدلازMechanistic target of rapamycin - هدف مکانیکی رپامایسینhistone deacetylase - هیستون داستیلازAMP-dependent protein kinase - پروتئین کیناز وابسته به AMP
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chemotherapy remains the most prescribed anti-cancer therapy, despite patients suffering severe side effects and frequently developing chemoresistance. These complications can be partially overcome by combining different chemotherapeutic agents that target multiple biological pathways. However, selecting efficacious drug combinations remains challenging. We previously used fission yeast Schizosaccharomycespombe as a surrogate model to predict drug combinations, and showed that suberoylanilide hydroxamic acid (SAHA) and cisplatin can sensitise gastric adenocarcinoma cells toward the cytotoxic effects of doxorubicin. Yet, how this combination undermines cell viability is unknown. Here, we show that SAHA and doxorubicin markedly enhance the cleavage of two apoptosis markers, caspase 3 and poly-ADP ribose polymerase (PARP-1), and increase the phosphorylation of γH2AX, a marker of DNA damage. Further, we found a prominent reduction in Ser485 phosphorylation of AMP-dependent protein kinase (AMPK), and reductions in its target mTOR and downstream ribosomal protein S6 phosphorylation. We show that SAHA contributes most of the effect, as confirmed using another histone deacetylase inhibitor, trichostatin A. Overall, our results show that the combination of SAHA and doxorubicin can induce apoptosis in gastric adenocarcinoma in a synthetically lethal manner, and that fission yeast offers an efficient tool for identifying potent drug combinations against human cancer cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 370, Issue 2, 15 September 2018, Pages 283-291
Journal: Experimental Cell Research - Volume 370, Issue 2, 15 September 2018, Pages 283-291
نویسندگان
Kwi Shan Seah, Jian Yun Loh, Thi Thuy Trang Nguyen, Hwei Ling Tan, Paul E. Hutchinson, Kim Kiat Lim, Brian W. Dymock, Yun Chau Long, Edmund Jon Deoon Lee, Han-Ming Shen, Ee Sin Chen,