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Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers

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dc.contributor.author Li, Feng
dc.contributor.author Shanmugam, Muthu K.
dc.contributor.author Siveen, Kodappully Sivaraman
dc.contributor.author Wang, Fan
dc.contributor.author Ong, Tina H.
dc.contributor.author Loo, Ser Yue
dc.contributor.author Swamy, Mahadeva M. M.
dc.contributor.author Mandal, Somnath
dc.contributor.author Kumar, Alan Prem
dc.contributor.author Goh, Boon Cher
dc.contributor.author Kundu, Tapas Kumar
dc.contributor.author Ahn, Kwang Seok
dc.contributor.author Wang, Ling Zhi
dc.contributor.author Hui, Kam Man
dc.contributor.author Sethi, Gautam
dc.date.accessioned 2016-10-28T06:01:30Z
dc.date.available 2016-10-28T06:01:30Z
dc.date.issued 2015
dc.identifier.citation Oncotarget en_US
dc.identifier.citation 6 en_US
dc.identifier.citation 7 en_US
dc.identifier.citation Li, F.; Shanmugam, M. K.; Siveen, K. S.; Wang, F.; Ong, T. H.; Loo, S. Y.; Swamy, M. M. M.; Mandal, S.; Kumar, A. P.; Goh, B. C.; Kundu, T.; Ahn, K. S.; Wang, L. Z.; Hui, K. M.; Sethi, G., Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers. Oncotarget 2015, 6 (7), 5147-5163. en_US
dc.identifier.issn 1949-2553
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/1930
dc.description Restricted access en_US
dc.description.abstract Platinum compounds such as cisplatin and carboplatin are frequently used as the first-line chemotherapy for the treatment of the head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated whether garcinol, a polyisoprenylated benzophenone can chemosensitize HNSCC to cisplatin. We found that garcinol inhibited the viability of a panel of diverse HNSCC cell lines, enhanced the apoptotic effect of cisplatin, suppressed constitutive as well as cisplatin-induced NF-kappa B activation, and downregulated the expression of various oncogenic gene products (cyclin D1, Bcl-2, survivin and VEGF). In vivo study showed that administration of garcinol alone (0.5 mg/kg body weight, i.p. five times/week) significantly suppressed the growth of the tumor, and this effect was further increased by cisplatin. Both the markers of proliferation index (Ki-67) and microvessel density (CD31) were downregulated in tumor tissues by the combination of cisplatin and garcinol. The pharmacokinetic results of garcinol indicated that good systemic exposure was achievable after i.p. administration of garcinol at 0.5 mg/kg and 2 mg/kg with mean peak concentration (Cmax) of 1825.4 and 6635.7 nM in the mouse serum, respectively. Overall, our results suggest that garcinol can indeed potentiate the effects of cisplatin by negative regulation of various inflammatory and proliferative biomarkers. en_US
dc.language.iso English en_US
dc.publisher Impact Journals LLC en_US
dc.rights ?Impact Journals LLC, 2015 en_US
dc.subject Oncology en_US
dc.subject Cell Biology en_US
dc.subject HNSCC en_US
dc.subject chemoresistance en_US
dc.subject NF-kappa B en_US
dc.subject proliferation en_US
dc.subject garcinol en_US
dc.subject Nf-Kappa-B en_US
dc.subject Squamous-Cell Carcinoma en_US
dc.subject Pancreatic Adenocarcinoma Cells en_US
dc.subject Gene-Expression en_US
dc.subject Cancer Cells en_US
dc.subject In-Vitro en_US
dc.subject Polyisoprenylated Benzophenone en_US
dc.subject Molecular-Mechanisms en_US
dc.subject Activation en_US
dc.subject Resistance en_US
dc.title Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers en_US
dc.type Article en_US


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