Structurally related ganoderic acids induce apoptosis in human cervical cancer HeLa cells: Involvement of oxidative stress and antioxidant protective system.
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 μM) 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 ≈ 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.
Guizhou Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, 563000, PR China.
Ru-Ming
RM
Liu
Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China.
Ying-Bo
YB
Li
Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China.
Xiang-Feng
XF
Liang
Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China.
Hui-Zhou
HZ
Liu
Guizhou Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, 563000, PR China. Electronic address: jianhuixiao@126.com.
Jian-Hui
JH
Xiao
State Key Laboratory of Microbial Metabolism, and Laboratory of Molecular Biochemical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai 200240, PR China. Electronic address: jjzhong@sjtu.edu.cn.
Jian-Jiang
JJ
Zhong
D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species; D014315:Triterpenes / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014315:Triterpenes; C556862:ganoderic acid
Acetylation; Antioxidant defense system; Cell apoptosis; Ganoderic acid; Ganoderma lucidum; Reactive oxygen species