期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 240, 期 -, 页码 134-144出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2015.08.005
关键词
Ganoderma lucidum; Ganoderic acid; Reactive oxygen species; Acetylation; Cell apoptosis; Antioxidant defense system
资金
- National Natural Science Foundation of China [30270038, 20776084]
- Shanghai Science & Technology Commission [054319933, 08DZ1971900]
- Guizhou High-Level Innovative Talent Support Program [QKH-RC-20154028]
- Program for Innovative Research Team in Guizhou Province [QKH-RCTD-20134035]
- Honghuagang district Science and Technology Project, Zunyi [2014-12]
Ganoderic acids (GAs) produced by Ganoderma lucidum possess anticancer activities with the generation of reactive oxygen species (ROS). However, the role of oxidative stress in apoptotic process induced by GAs is still undefined. In this study, the effects of four structurally related GAs, i.e. GA-T, GA-Mk, and two deacetylated derivatives of GA-T (GA-T1 and GA-T2) on the antioxidant defense system and induced apoptosis in cervical cancer cells HeLa were investigated in vitro. Our results indicated that the tested GAs (5-40 mu M) induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9 and caspase-3. Furthermore. GAs increased the generation of intracellular ROS and attenuated antioxidant defense system by decreasing glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities. The above effects were remarkably blocked by the exogenous antioxidants, i.e. N-acetylcysteine, catalase and diphenyleneiodonium chloride. The potency of the four GAs toward induced apoptosis, generation of ROS and suppression of antioxidant defense system was in the order of: GA-T > GA-Mk approximate to GA-T1 > GA-T2 in HeLa cells. These findings suggest that GAs induced mitochondria-dependent cell apoptosis in HeLa cells are mediated via enhancing oxidative stress and depressing antioxidant defense. Additionally, the acetylation of hydroxyl groups in GAs may contribute to their pro-oxidant activities and cytotoxicity, which is helpful to the development of novel chemotherapy agents. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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