Effect of silibinin in human colorectal cancer cells: Targeting the activation of NF‐κB signaling. Issue 3 (15th November 2011)

• Record Type: Journal Article
• Authors: Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh
• Is Part Of: Molecular carcinogenesis. Volume 52:Issue 3(2013:Mar.)
• Page Start: 195
• Page End: 206
• Publication Date: 2011-11-15
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.21843
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Chronic inflammation is one of the primary causes of colorectal cancer (CRC), and major inflammatory pathways implicated in CRC are cyclooxygenase‐2 (COX‐2) and iNOS; both regulated by nuclear factor‐kappa B (NF‐κB) suggesting that inhibitors of these pathways could be ideal against CRC. Silibinin has shown promising efficacy against various malignancies including CRC, and therefore here we assessed whether silibinin targets NF‐κB activation and associated signaling as a mechanism of its anti‐inflammatory and anti‐cancer effects in CRC. Our results indicated that silibinin treatment (50–200 µM) of human CRC SW480, LoVo, and HT29 cells strongly inhibits tumor necrosis factor α‐induced NF‐κB activation together with decreased nuclear levels of both p65 and p50 sub‐units. Silibinin also significantly increased IκBα level with a concomitant decrease in phospho‐IκBα, without any effect on TNFR1, TRADD, and RIP2, indicating its inhibitory effect on IκB kinase α activity. Next we assessed the effect of oral silibinin feeding on NF‐κB pathway in SW480 (COX‐2 negative) and LoVo (COX‐2 positive) tumor xenografts in nude mice. Together with its inhibitory efficacy on tumor growth and progression, silibinin inhibited NF‐κB activation in both xenografts. The protein levels of various NF‐κB‐regulated molecules such as Bcl‐2, COX‐2, iNOS, VEGF, and MMPs were also decreased by silibinin in both cell culture studies and xenograft analyses, suggesting its potential to alter NF‐κB transcriptional activity. Together, these findings are highly significant in establishing for the first time that silibinin suppresses CRC growth and progression possibly through its anti‐inflammatory activity by interfering with NF‐κB activation and thus has potential against human CRC. © 2011 Wiley Periodicals, Inc.</p> </abstract>