کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10899638 | 1084398 | 2014 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
SKLB316, a novel small-molecule inhibitor of cell-cycle progression, induces G2/M phase arrest and apoptosis in vitro and inhibits tumor growth in vivo
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کلمات کلیدی
FCM3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromideCHK2PVDFRh123CDK1ΔΨmPMSFDMSO - DMSOMTT - MTTROS - ROSstandard deviation - انحراف معیارTerminal deoxynucleotidyl transferase dUTP nick end labeling - ترمینال deoxynucleotidyl transferase dUTP نام نهایی پایان نامهCell cycle arrest - توقف چرخه سلولیTUNEL - تونلApoptosis - خزان یاختهایpolyvinylidene difluoride - دی فلوئورید پلی وینیلیدینDimethyl sulfoxide - دیمتیل سولفواکسیدRhodamine-123 - رودامین 123Anti-cancer - ضدسرطانFlow cytometry - فلوسیتومتریphenylmethylsulfonyl fluoride - فنیل متیل سولفونیل فلورایدMitochondrial membrane potential - پتانسیل غشای میتوکندریPropidium iodide - پروتئین یدیدDrug discovery - کشف مواد مخدرCyclin-dependent kinase 1 - کیناز وابسته به سیکلین 1Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Benzothiazole derivatives have received considerable attentions for their potencies in cancer therapy. In the present study, we reported that SKLB316, a novel synthesized benzothiazole derivative, exhibits activities to inhibit colorectal and pancreatic cancer in vitro and in vivo by inducing G2/M cell cycle arrest and apoptosis. In vitro, it exhibited significant anti-proliferative activities against human cancer cells derived from different histotypes including the colorectal cancer cell line HCT116 and pancreatic cancer cell line CFPAC-1. We chose these cell lines to study the possible anti-tumor mechanism because they are sensitive to SKLB316 treatment. Flow cytometry assays showed that SKLB316 could induce G2/M cell cycle arrest. Mechanistically, SKLB316 could decrease the activities of cdc2/cyclin B1 complex, including decreasing the synthesis of cyclin B1, cdc2 and cdc25c, while accumulating the levels of phosphorylated cdc2 (Tyr15) and checkpoint kinase 2. SKLB316 could also decrease the level of cyclin E and A2. Moreover, SKLB316 could induce cancer cell apoptosis, which was associated with activation of caspase 9, downregulation of Bcl-2 and upregulation of Bax. SKLB316 could also decrease the mitochondrial membrane potential and induce the generation of reactive oxygen species in cells. The results implied that SKLB316 may induce apoptosis via the mitochondria-mediated apoptotic pathway. Moreover, SKLB316 could suppress the growth of established colorectal and pancreatic cancer tumors in nude mice without causing obvious side effects. TUNEL assays confirmed that SKLB316 could also induce tumor cell apoptosis in vivo. Taken together, these findings demonstrate the potential value of SKLB316 as a novel anti-tumor drug candidate.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 355, Issue 2, 28 December 2014, Pages 297-309
Journal: Cancer Letters - Volume 355, Issue 2, 28 December 2014, Pages 297-309
نویسندگان
Yong Xia, Qian Lei, Yongxia Zhu, Tinghong Ye, Ningyu Wang, Guobo Li, Xuanhong Shi, Yantong Liu, Bin Shao, Tao Yin, Lifeng Zhao, Wenshuang Wu, Xuejiao Song, Ying Xiong, Yuquan Wei, Luoting Yu,