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

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 cisplat...

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Autores principales: 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, Ahn, Kwang Seok, Wang, Ling Zhi, Hui, Kam Man, Sethi, Gautam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467139/
https://www.ncbi.nlm.nih.gov/pubmed/25762616
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author 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
Ahn, Kwang Seok
Wang, Ling Zhi
Hui, Kam Man
Sethi, Gautam
author_facet 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
Ahn, Kwang Seok
Wang, Ling Zhi
Hui, Kam Man
Sethi, Gautam
author_sort Li, Feng
collection PubMed
description 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-κB 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.
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spelling pubmed-44671392015-06-22 Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers 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 Ahn, Kwang Seok Wang, Ling Zhi Hui, Kam Man Sethi, Gautam Oncotarget Research Paper 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-κB 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. Impact Journals LLC 2015-02-28 /pmc/articles/PMC4467139/ /pubmed/25762616 Text en Copyright: © 2015 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
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
Ahn, Kwang Seok
Wang, Ling Zhi
Hui, Kam Man
Sethi, Gautam
Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
title Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
title_full Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
title_fullStr Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
title_full_unstemmed Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
title_short Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
title_sort garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467139/
https://www.ncbi.nlm.nih.gov/pubmed/25762616
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