DSpace Repository

Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo

Show simple item record

dc.contributor.author Sethi, Gautam
dc.contributor.author Chatterjee, Snehajyoti
dc.contributor.author Rajendran, Peramaiyan
dc.contributor.author Li, Feng
dc.contributor.author Shanmugam, Muthu K.
dc.contributor.author Wong, Kwong Fai
dc.contributor.author Kumar, Alan Prem
dc.contributor.author Senapati, Parijat
dc.contributor.author Behera, Amit K.
dc.contributor.author Hui, Kam Man
dc.contributor.author Basha, Jeelan
dc.contributor.author Natesh, Nagashayana
dc.contributor.author Luk, John M.
dc.contributor.author Kundu, Tapas Kumar
dc.date.accessioned 2017-02-17T05:09:16Z
dc.date.available 2017-02-17T05:09:16Z
dc.date.issued 2014
dc.identifier.citation Sethi, G; Chatterjee, S; Rajendran, P; Li, F; Shanmugam, MK; Wong, KF; Kumar, AP; Senapati, P; Behera, AK; Hui, KM; Basha, J; Natesh, N; Luk, JM; Kundu, TK, Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo. Molecular Cancer 2014, 13, 66 http://dx.doi.org/10.1186/1476-4598-13-66 en_US
dc.identifier.citation Molecular Cancer en_US
dc.identifier.citation 13 en_US
dc.identifier.issn 1476-4598
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/2334
dc.description Open Access en_US
dc.description.abstract Background: Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been linked with proliferation, survival, invasion and angiogenesis of a variety of human cancer cells, including hepatocellular carcinoma (HCC). Thus, novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. Here we report, garcinol, a polyisoprenylated benzophenone, could suppress STAT3 activation HCC cell lines and in xenografted tumor of HCC in nude mice model. Experimental design: Different HCC cell lines have been treated with garcinol and the inhibition of STAT3 activation, dimerization and acetylation have been checked by immunoblotting, immuno-fluorescence, and DNA binding assays. Xenografted tumor model has been generated in nude mice using HCC cell line and effect of garcinol in the inhibition of tumor growth has been investigated. Results: Garcinol could inhibit both constitutive and interleukin (IL-6) inducible STAT3 activation in HCC cells. Computational modeling showed that garcinol could bind to the SH2 domain of STAT3 and suppress its dimerization in vitro. Being an acetyltransferase inhibitor, garcinol also inhibits STAT3 acetylation and thus impairs DNA binding ability. The inhibition of STAT3 activation by garcinol led to the suppression of expression of various genes involved in proliferation, survival, and angiogenesis. It also suppressed proliferation and induced substantial apoptosis in HCC cells. Remarkably, garcinol inhibited the growth of human HCC xenograft tumors in athymic nu/nu mice, through the inhibition of STAT3 activation. Conclusion: Overall, our results suggest that garcinol exerts its anti-proliferative and pro-apoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo. en_US
dc.description.uri http://dx.doi.org/10.1186/1476-4598-13-66 en_US
dc.language.iso English en_US
dc.publisher Biomed Central Ltd en_US
dc.rights @Biomed Central Ltd, 2014 en_US
dc.subject Biochemistry & Molecular Biology en_US
dc.subject Oncology en_US
dc.subject Hcc en_US
dc.subject Stat3 en_US
dc.subject Acetylation en_US
dc.subject Garcinol en_US
dc.subject Apoptosis en_US
dc.subject Global Gene-Expression en_US
dc.subject Signal Transducer en_US
dc.subject Cancer Cells en_US
dc.subject Polyisoprenylated Benzophenone en_US
dc.subject Down-Regulation en_US
dc.subject Apoptosis en_US
dc.subject Transcription en_US
dc.subject Survival en_US
dc.subject Activation en_US
dc.subject Histone en_US
dc.title Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo en_US
dc.type Article en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account