کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5846410 | 1128479 | 2013 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways
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کلمات کلیدی
NF-E2 p45-related factor 2Heme oxygenase-1IκBαIKKPGE2ECMiNOSCOX-2HO-1phorbol 12-myristate 13-acetateNrf2NQO1NAD(P)H quinone oxidoreductase-1Nrf2-Keap1MMPNF-κBShogaolskeap1 - buy1IκB kinase - IkB kinasePMA - LDC هاGinger - زنجبیلinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییCyclooxygenase-2 - سیکلوکوکسیژناز2antioxidant response element - عنصر پاسخ آنتی اکسیدانnuclear factor-κB - فاکتور هسته ای κBExtracellular matrix - ماتریکس خارج سلولیmatrix metalloproteinase - ماتریکس متالوپروتئینازARE - هستندMichael acceptors - پذیرندگان مایکلKelch-like ECH-associated protein 1 - پروتئین مرتبط با ECH کلچ 1Chemoprevention - پیشگیری شیمیایی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways](/preview/png/5846410.png)
چکیده انگلیسی
Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E2 (PGE2) in RAW 264.7 macrophage-like cells. Inhibition of cancer cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 272, Issue 3, 1 November 2013, Pages 852-862
Journal: Toxicology and Applied Pharmacology - Volume 272, Issue 3, 1 November 2013, Pages 852-862
نویسندگان
Fei-Fei Gan, Hui Ling, Xiaohui Ang, Shridhivya A. Reddy, Stephanie S-H. Lee, Hong Yang, Sock-Hoon Tan, John D. Hayes, Wai-Keung Chui, Eng-Hui Chew,