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Title: Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
Authors: Li, Feng
Shanmugam, Muthu K.
Siveen, Kodappully Sivaraman
Wang, Fan
Ong, Tina H.
Loo, Ser Yue
Swamy, Mahadeva M. M.
Mandal, Somnath
Kumar, Alan Prem
Goh, Boon Cher
Kundu, Tapas Kumar
Ahn, Kwang Seok
Wang, Ling Zhi
Hui, Kam Man
Sethi, Gautam
Keywords: Oncology
Cell Biology
NF-kappa B
Squamous-Cell Carcinoma
Pancreatic Adenocarcinoma Cells
Cancer Cells
Polyisoprenylated Benzophenone
Issue Date: 2015
Publisher: Impact Journals LLC
Citation: Oncotarget
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.
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.
Description: Restricted access
ISSN: 1949-2553
Appears in Collections:Research Papers (Tapas K. Kundu)

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