کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5562540 | 1562701 | 2017 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Withaferin A induced impaired autophagy and unfolded protein response in human breast cancer cell-lines MCF-7 and MDA-MB-231
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کلمات کلیدی
autophagy protein 5AVOssequestosome 1SQSTM1ATG5EtBrLC3MDCER-stress - ER-استرسAcridine orange - آکاردین نارنجیethidium bromide - اتیدیوم برومایدAcidic vesicular organelles - اندام های حسی اسیدیwithaferin A - با aaaferin ABreast cancer - سرطان پستانUbiquitin-proteasome system - سیستم Ubiquitin-proteasomewortmannin - ورتمنینUnfolded protein response - پاسخ پروتئین آشکارchymotrypsin - کیموتریپسینUPS - یو پی اس
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The autophagy-lysosome pathway and the ubiquitin-proteasome systems are the two major routes for eukaryotic intracellular protein clearance. Cancerous cells often display elevated protein synthesis and byproduct disposal, thus, inhibition of the protein degradation pathways became an emerging approach for cancer therapy. The present study revealed that withaferin-A (WA), the biologically active withanolide derived from Withania somnifera, initially induced formation of autophagosomes in human breast cancer cell-lines, MCF-7 and MDA-MB-231. WA treatment elevated the levels of autophagic substrate p62/SQSTM1 (p62) and both LC3-II and LC3-I (microtubule-associated protein 2 light chain 3) and simultaneously reduced the upstream autophagy markers like beclin-1 and ATG5-ATG12 complex, which indicate accumulation of autophagosomes in the cells. WA induced disruption of microtubular network through inhibition of tubulin polymerization and its hyper-acetylation, thus prevent the formation of autolysosome (by merging of autophagosomes with lysosomes) and its recycling process, leading to incomplete autophagy. Further, WA caused ER (Endoplasmic Reticulum) stress, which is evident from the activation of ER-related caspase-4 and increased levels of ER stress marker proteins. Thus, these findings altogether indicate that WA mediated inhibition of proteasomal degradation system and perturbation of autophagy, i.e. suppression of both the intracellular degradation systems caused accumulation of ubiquitinated proteins, which in turn led to unfolded protein response and ER stress mediated proteotoxicity in human breast cancer cell-lines, MCF-7 and MDA-MB-231.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 44, October 2017, Pages 330-338
Journal: Toxicology in Vitro - Volume 44, October 2017, Pages 330-338
نویسندگان
Kamalini Ghosh, Soumasree De, Srimoyee Mukherjee, Sayantani Das, Amar Nath Ghosh, Sumita (Bandyopadhyay) Sengupta,