Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.2881
Title: Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
Authors: 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. 
Keywords: antineoplastic agent
benzophenone derivative
cisplatin
cyclin D1
garcinol
immunoglobulin enhancer binding protein
Ki 67 antigen
protein bcl 2
survivin
tumor marker
unclassified drug
vasculotropin
antineoplastic agent
biological marker
cisplatin
garcinol
messenger RNA
plant extract
terpene
animal cell
animal experiment
animal model
animal tissue
apoptosis
area under the curve
Article
cancer combination chemotherapy
cancer inhibition
cancer model
capillary density
carcinoma cell
cell viability
chemosensitization
controlled study
down regulation
drug absorption
drug blood level
drug exposure
drug potentiation
female
gene expression regulation
gene product
head and neck carcinoma
histopathology
human
human cell
in vivo study
maximum plasma concentration
monotherapy
mouse
nonhuman
systemic therapy
transcription initiation
tumor xenograft
\garcinol
animal
Carcinoma, Squamous Cell
cell proliferation
down regulation
drug effects
drug potentiation
drug screening
enzyme immunoassay
genetics
Head and Neck Neoplasms
metabolism
nude mouse
pathology
real time polymerase chain reaction
reverse transcription polymerase chain reaction
signal transduction
tumor cell culture
Western blotting
Animals
Antineoplastic Agents
Apoptosis
Biomarkers
Blotting, Western
Carcinoma, Squamous Cell
Cell Proliferation
Cisplatin
Down-Regulation
Drug Synergism
Female
Head and Neck Neoplasms
Humans
Immunoenzyme Techniques
Mice
Mice, Nude
Plant Extracts
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
Signal Transduction
Terpenes
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Issue Date: 2015
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. (2015). Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers. Oncotarget 6 (7) : 5147-5163. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.2881
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-?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.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/174150
ISSN: 19492553
DOI: 10.18632/oncotarget.2881
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