Cedrol, a Sesquiterpene Alcohol, Enhances the Anticancer Efficacy of Temozolomide in Attenuating Drug Resistance via Regulation of the DNA Damage Response and MGMT Expression

doi:10.1021/acs.jnatprod.0c00580

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24480

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24480

Title:	Cedrol, a Sesquiterpene Alcohol, Enhances the Anticancer Efficacy of Temozolomide in Attenuating Drug Resistance via Regulation of the DNA Damage Response and MGMT Expression
Authors:	Chang, KF;Huang, XF;Chang, JT;Huang, YC;Lo, WS;Hsiao, CY;Tsai, NM
Date:	2020
Issue Date:	2022-08-09T08:03:02Z (UTC)
Publisher:	AMER CHEMICAL SOC
ISSN:	0163-3864
Abstract:	Glioblastoma (GBM) is a common and aggressive brain tumor with a median survival of 12-15 months. Temozolomide (TMZ) is a first-line chemotherapeutic agent used in GBM therapy, but the occurrence of drug resistance limits its antitumor activity. The natural compound cedrol has remarkable antitumor activity and is derived from Cedrus atlantica. In this study, we investigated the combined effect of TMZ and cedrol in GBM cells in vitro and in vivo. The TMZ and cedrol combination treatment resulted in consistently higher suppression of cell proliferation via regulation of the AKT and MAPK signaling pathways in GBM cells. The combination treatment induced cell cycle arrest, cell apoptosis, and DNA damage better than either drug alone. Furthermore, cedrol reduced the expression of proteins associated with drug resistance, including O-6-methlyguanine-DNA-methyltransferase (MGMT), multidrug resistance protein 1 (MDR1), and CD133 in TMZ-treated GBM cells. In the animal study, the combination treatment significantly suppressed tumor growth through the induction of cell apoptosis and decreased TMZ drug resistance. Moreover, cedrol-treated mice exhibited no significant differences in body weight and improved TMZ-induced liver damage. These results imply that cedrol may be a potential novel agent for combination treatment with TMZ for GBM therapy that deserves further investigation.
URI:	http://dx.doi.org/10.1021/acs.jnatprod.0c00580 https://www.webofscience.com/wos/woscc/full-record/WOS:000586023100021 https://ir.csmu.edu.tw:8080/handle/310902500/24480
Relation:	JOURNAL OF NATURAL PRODUCTS ,2020 ,v83 ,issue 10 ,p3021-3029
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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