کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5525692 | 1546681 | 2017 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Trichodermin induces c-Jun N-terminal kinase-dependent apoptosis caused by mitotic arrest and DNA damage in human p53-mutated pancreatic cancer cells and xenografts
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
CDCdual specificity protein phosphatase 1DUSP1Bcl-xLDSBsBcl-2Mcl-1JnkMMPCDKc-Jun N-terminal kinase - C-Jun N-terminal kinaseDNA damage - آسیبDNAIHC - ایمونوهیستوشیمیimmunohistochemical - ایمونوهیستوشیمیApoptosis - خزان یاختهایMitotic arrest - دستگیری متیوتیکPancreatic cancer - سرطان پانکراسdouble-strand breaks - شکست دو ردیفB-cell lymphoma 2 - لنفوم سلول B 2Myeloid cell leukemia 1 - لوسمی سلول میلوئید 1Mitochondrial membrane potential - پتانسیل غشای میتوکندریCell division cycle - چرخه تقسیم سلولیcyclin-dependent kinase - کییناز وابسته به سیکلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Pancreatic cancer is an aggressive malignancy, which generally responds poorly to chemotherapy. In this study, trichodermin, an endophytic fungal metabolite from Nalanthamala psidii, was identified as a potent and selective antitumor agent in human pancreatic cancer. Trichodermin exhibited antiproliferative effects against pancreatic cancer cells, especially p53-mutated cells (MIA PaCa-2 and BxPC-3) rather than normal pancreatic epithelial cells. We found that trichodermin induced caspase-dependent and mitochondrial intrinsic apoptosis. Trichodermin also increased apoptosis through mitotic arrest by activating Cdc2/cyclin B1 complex activity. Moreover, trichodermin promoted the activation of c-Jun N-terminal kinase (JNK), and inhibition of JNK by its inhibitor, shRNA, or siRNA significantly reversed trichodermin-mediated caspase-dependent apoptosis. Trichodermin triggered DNA damage stress to activate p53 function for executing apoptosis in p53-mutated cells. Importantly, we demonstrated that trichodermin with efficacy similar to gemcitabine, profoundly suppressed tumor growth through inducing intratumoral DNA damage and JNK activation in orthotopic pancreatic cancer model. Based on these findings, trichodermin is a potential therapeutic agent worthy of further development into a clinical trial candidate for treating cancer, especially the mutant p53 pancreatic cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 388, 1 March 2017, Pages 249-261
Journal: Cancer Letters - Volume 388, 1 March 2017, Pages 249-261
نویسندگان
Ming-Hsien Chien, Tzong-Huei Lee, Wei-Jiunn Lee, Yen-Hsiu Yeh, Tsai-Kun Li, Po-Chuan Wang, Jih-Jung Chen, Jyh-Ming Chow, Yung-Wei Lin, Michael Hsiao, Shih-Wei Wang, Kuo-Tai Hua,