文献类型：期刊文献

英文题名：Cytotoxic and pro-apoptotic effects of novel ganoderic acid derivatives on human cervical cancer cells in vitro

作者：Liu, Ru-Ming[1];Li, Ying-Bo[1];Zhong, Jian-Jiang[1,2]

机构：[1]E China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China

年份：2012

卷号：681

期号：1-3

起止页码：23

外文期刊名：EUROPEAN JOURNAL OF PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000301799400004)】；

基金：Financial support from the National Natural Science Foundation of China (no. 30821005), the Shanghai Science & Technology Commission (project nos. 054319933 and 08DZ1971900), and the Shanghai Leading Academic Discipline Project (project nos. B203 and B505) is gratefully acknowledged.

语种：英文

外文关键词：Ganoderma lucidum; Ganoderic acid derivative; Cervical cancer; Cell apoptosis; Mitochondrial membrane potential; Caspase

摘要：Ganoderic acid T, a triterpenic acid produced by Ganoderma lucidum, has demonstrated therapeutic potential for tumor disease. In the current work, ganoderic acid T was modified to produce more effective smallmolecule inhibitors of cancer cell proliferation. Moreover, the anticancer effects of three new ganoderic acid T derivatives, i. e., (22S, 24E)-3a, 15a, 22-triacetoxy-5a-lanosta-7,9(11), 24-trien-26-oic acid ethyl ester (TLTO-Ee), (22S, 24E)-3a, 15a, 22-triacetoxy-5a-lanosta-7,9(11), 24-trien-26-oic acid propyl ester (TLTO-Pe), and (22S, 24E)-3a, 15a, 22-triacetoxy-5a-lanosta-7,9(11), 24-trien-26-oic acid amide (TLTO-A), and one known derivative, (22S, 24E)-3a, 15a, 22-triacetoxy-5a-lanosta-7,9(11), 24-trien-26-oic acid methyl ester (TLTO-Me), on the cervical cell line HeLawere investigated and compared. MTT assay indicated that, among the tested compounds, TLTO-A displayed the highest inhibitory effect on the growth of HeLa cells, whereas it showed less cytotoxicity to the non-tumorous cell line MCF-10A than ganoderic acid T. Flow cytometry analysis revealed that all the compounds caused cell cycle arrest at the G1 phase and induced apoptosis. Furthermore, they decreased the mitochondrialmembrane potential and enhanced the activities of pro-apoptotic factors caspase-3 and caspase-9 in a dose-dependentmanner. Accordingly, the apoptosis induction was presumed to occur through the endogenous pathway. The following order ranks both cytotoxic and pro-apoptotic effects of the compounds against HeLa cells: TLTO-A> ganoderic acid T approximate to TLTO-Me approximate to TLTO-Ee approximate to TLTO-Pe. This study suggests that the carboxyl group of ganoderic acid T is not the main active group and is suitable for its further structural modification. The current work presents valuable information on the design of ganoderic acid T derivatives to develop potential chemotherapy agents. (C) 2012 Elsevier B. V. All rights reserved.