کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9001897 | 1118561 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Curcumin (diferuloylmethane) inhibits constitutive NF-κB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma
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کلمات کلیدی
NF-κBEMSAinhibitory subunit of NF-κBNF-κB essential modifier3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromideNBDIκBαIKKPMSFPTDNEMOFBSHRPMCLPISIκB kinase - IkB kinaseMTT - MTTElectrophoretic mobility shift assay - آزمون تحرک تحرک الکتروفورزEBV - اپشتین بار ویروسProtein transduction domain - دامنه انتقال پروتئینfetal bovine serum - سرم جنین گاوNuclear transcription factor-κB - فاکتور رونویسی هسته ای κBphenylmethylsulfonyl fluoride - فنیل متیل سولفونیل فلورایدMantle cell lymphoma - لنفوم سلول انسانیEpstein-Barr virus - ویروس Epstein-Barrhorse radish peroxidase - پراکسیداز تربچه اسبPropidium iodide - پروتئین یدیدCurcumin - کورکومین
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
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چکیده انگلیسی
Human mantle cell lymphoma (MCL), an aggressive B cell non-Hodgkin's lymphoma, is characterized by the overexpression of cyclin D1 which plays an essential role in the survival and proliferation of MCL. Because of MCL's resistance to current chemotherapy, novel approaches are needed. Since MCL cells are known to overexpress NF-κB regulated gene products (including cyclin D1), we used curcumin, a pharmacologically safe agent, to target NF-κB in a variety of MCL cell lines. All four MCL cell lines examined had overexpression of cyclin D1, constitutive active NF-κB and IκB kinase and phosphorylated forms of IκBα and p65. This correlated with expression of TNF, IκBα, Bcl-2, Bcl-xl, COX-2 and IL-6, all regulated by NF-κB. On treatment of cells with curcumin, however, downregulated constitutive active NF-κB and inhibited the consitutively active IκBα kinase (IKK), and phosphorylation of IκBα and p65. Curcumin also inhibited constitutive activation of Akt, needed for IKK activation. Consequently, the expression of all NF-κB-regulated gene products, were downregulated by the polyphenol leading to the suppression of proliferation, cell cycle arrest at the G1/S phase of the cell cycle and induction of apoptosis as indicated by caspase activation, PARP cleavage, and annexin V staining. That NF-κB activation is directly linked to the proliferation of cells, is also indicated by the observation that peptide derived from the IKK/NEMO-binding domain and p65 suppressed the constitutive active NF-κB complex and inhibited the proliferation of MCL cells. Constitutive NF-κB activation was found to be due to TNF, as anti-TNF antibodies inhibited both NF-κB activation and proliferation of cells. Overall, our results indicate that curcumin inhibits the constitutive NF-κB and IKK leading to suppression of expression of NF-κB-regulated gene products that results in the suppression of proliferation, cell cycle arrest, and induction of apoptosis in MCL.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 70, Issue 5, 1 September 2005, Pages 700-713
Journal: Biochemical Pharmacology - Volume 70, Issue 5, 1 September 2005, Pages 700-713
نویسندگان
Shishir Shishodia, Hesham M. Amin, Raymond Lai, Bharat B. Aggarwal,