Vitexin abrogates invasion and survival of hepatocellular carcinoma cells through targeting STAT3 signaling pathway

Lee, Jong Hyun and Mohan, Chakrabhavi Dhananjaya and Shanmugam, Muthu K. and Rangappa, Shobith and Sethi, Gautam and Siveen, Kodappully Sivaraman and Chinnathambi, Arunachalam and Alahmadi, Tahani Awad and Alharbi, Sulaiman Ali and Basappa, Salundi and Rangappa, Kanchugarakoppal S. and Ahn, Kwang Seok (2020) Vitexin abrogates invasion and survival of hepatocellular carcinoma cells through targeting STAT3 signaling pathway. Biochimie, 175. pp. 58-68. ISSN 1638-6183

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Hepatocellular carcinoma (HCC) is a major malignancy that stands second in terms of global cancer-related mortality. STAT3 has been described as a latent transcription factor that promotes tumorigenesis. This study was designed to examine the effect of vitexin on STAT3 signaling and important hallmarks of cancer. HCC cells were employed to decipher the impact of vitexin on activation of STAT3 signaling using Western blotting, EMSA, immunocytochemistry, and reporter assay. The combinational apoptotic effects of vitexin with approved anti-cancer drugs was examined by live-dead assay, and its anti-invasive potential was studied using matrigel assay. The results obtained in cell-based assays were verified using in silico analysis. Vitexin effectively inhibited sustained activation of JAK1, JAK2, Src, and STAT3 in HCC cells. Vitexin downregulated DNA binding ability, reduced the nuclear pool of STAT3, and diminished epidermal growth factor (EGF)-driven STAT3 gene expression. Interestingly, treatment with tyrosine phosphatase inhibitor altered the vitexin-induced STAT3 phosphorylation, and the attenuation of STAT3 by vitexin was found to be driven through the upregulation of PTPeC. The combinational studies indicated that vitexin can exhibit substantial apoptotic effects with doxorubicin and sorafenib. It also suppressed the CXCL12-induced cell invasion. The results of cell-based assays are supported by in silico analysis as the vitexin displayed favorable interaction with kinase domain of JAK2 protein. Overall, this study demonstrated that vitexin can act as a potential blocker of the STAT3 signaling cascade and mitigate the survival as well as invasion of HCC cells. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Item Type: Article
Uncontrolled Keywords: HCC; STAT3; Apoptosis; Invasion; Migration; PTP
Subjects: B Life Science > Molecular Biology
Divisions: Department of > Molecular Biology
Depositing User: Mr Umendra uom
Date Deposited: 05 Mar 2021 06:18
Last Modified: 05 Mar 2021 06:18

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