Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2334
Title: Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo
Authors: Sethi, Gautam
Chatterjee, Snehajyoti
Rajendran, Peramaiyan
Li, Feng
Shanmugam, Muthu K.
Wong, Kwong Fai
Kumar, Alan Prem
Senapati, Parijat
Behera, Amit K.
Hui, Kam Man
Basha, Jeelan
Natesh, Nagashayana
Luk, John M.
Kundu, Tapas Kumar
Keywords: Biochemistry & Molecular Biology
Oncology
Hcc
Stat3
Acetylation
Garcinol
Apoptosis
Global Gene-Expression
Signal Transducer
Cancer Cells
Polyisoprenylated Benzophenone
Down-Regulation
Apoptosis
Transcription
Survival
Activation
Histone
Issue Date: 2014
Publisher: Biomed Central Ltd
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
Molecular Cancer
13
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.
Description: Open Access
URI: http://hdl.handle.net/10572/2334
ISSN: 1476-4598
Appears in Collections:Research Papers (Tapas K. Kundu)

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