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

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標題:	Cedrol, a Sesquiterpene Alcohol, Enhances the Anticancer Efficacy of Temozolomide in Attenuating Drug Resistance via Regulation of the DNA Damage Response and MGMT Expression
作者:	Chang, Kai-Fu Huang, Xiao-Fan Chang, Jinghua Tsai Huang, Ya-Chih Lo, Wei-Syuan Hsiao, Chih-Yen Tsai, Nu-Man
貢獻者:	Chung Shan Med Univ, Inst Med Chung Shan Med Univ, Dept Med Lab & Biotechnol Chung Shan Med Univ Hosp, Clin Lab Ditmanson Med Fdn, Dept Internal Med, Div Nephrol, Chia Yi Christian Hosp Chia Nan Univ Pharm & Sci, Dept Hosp & Hlth Care Adm
日期:	2020
上傳時間:	2022-11-18 11:23:48 (UTC+8)
出版者:	Amer Chemical Soc
摘要:	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.
關聯:	Journal of Natural Products, v.83, n.10, pp.9
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