کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8303881 | 1537956 | 2013 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Calix[6]arene bypasses human pancreatic cancer aggressiveness: Downregulation of receptor tyrosine kinases and induction of cell death by reticulum stress and autophagy
ترجمه فارسی عنوان
آرایش کالیکس [6] از تجاوز به سلول انسانی پانکراس جلوگیری می کند: کمینه سازی گیرنده های تیروزین کیناز و القای مرگ سلول ها توسط استرس رتیکولوم و اتوفایگی
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کلمات کلیدی
PI3KJnk2CTRLmTORHSP90Bcl2LC3PIMIRE1BiP - BIPCalix[6]arene - Calix [6] areneCDKs - CDK هاAkt - آکتAutophagy - اتوفاژیEndoplasmic reticulum stress - استرس شبکه آندوپلاسمیAxl - اکسلBax - باکسMER - بیشترretinoblastoma - رتینوبلاستوما، تومور شبکیهmicrotubule-associated protein light chain 3 - زنجیره سبک پروتئینی مرتبط با میکروتوبول 3Pancreatic cancer - سرطان پانکراسendoplasmic reticulum - شبکه آندوپلاسمی phosphoinositide 3-kinase - فسفینوزیتید 3-کینازBCL2-associated X protein - پروتئین X مرتبط با BCL2Binding immunoglobulin Protein - پروتئین ایمونوگلوبولین BindingHeat shock protein 90 - پروتئین شوک حرارت 90Chloroquine - کلروکین Clq - کلکControl - کنترلcyclin-dependent kinases - کیناز وابسته به سیکلینReceptor Tyrosine Kinase - گیرنده تیروزین کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Pancreatic cancer ranks fourth among cancer-related causes of death in North America. Minimal progress has been made in the diagnosis and treatment of patients with late-stage tumors. Moreover, pancreatic cancer aggressiveness is closely related to high levels of pro-survival mediators, which can ultimately lead to rapid disease progression, resistance and metastasis. The main goal of this study was to define the mechanisms by which calix[6]arene, but not other calixarenes, efficiently decreases the aggressiveness of a drug resistant human pancreas carcinoma cell line (Panc-1). Calix[6]arene was more potent in reducing Panc-1 cell viability than gemcitabine and 5-fluorouracil. In relation to the underlying mechanisms of cytotoxic effects, it led to cell cycle arrest in the G0/G1 phase through downregulation of PIM1, CDK2, CDK4 and retinoblastoma proteins. Importantly, calix[6]arene abolished signal transduction of Mer and AXL tyrosine kinase receptors, both of which are usually overexpressed in pancreatic cancer. Accordingly, inhibition of PI3K and mTOR was also observed, and these proteins are positively modulated by Mer and AXL. Despite decreasing the phosphorylation of AKT at Thr308, calix[6]arene caused an increase in phosphorylation at Ser473. These findings in conjunction with increased BiP and IRE1-α provide a molecular basis explaining the capacity of calix[6]arene to trigger endoplasmic reticulum stress and autophagic cell death. Our findings highlight calix[6]arene as a potential candidate for overcoming pancreatic cancer aggressiveness. Importantly, we provide evidence that calix[6]arene affects a broad array of key targets that are usually dysfunctional in pancreatic cancer, a highly desirable characteristic for chemotherapeutics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1833, Issue 12, December 2013, Pages 2856-2865
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1833, Issue 12, December 2013, Pages 2856-2865
نویسندگان
Karin Juliane Pelizzaro-Rocha, Marcelo Bispo de Jesus, Roberta Regina Ruela-de-Sousa, Celso Vataru Nakamura, Fabiano Souza Reis, Angelo de Fátima, Carmen VerÃssima Ferreira-Halder,