Timosaponin AIII induces apoptosis and autophagy in human melanoma A375-S2 cells.
Timosaponin AIII (AIII), a steroidal saponin isolated from Anemarrhena asphodeloides Bge. Our study showed that AIII induced both apoptosis and autophagy, and autophagy inhibited apoptosis in A375S2 cells. Furtherly, this study was carried out to investigate what kind of cytokines plays an important role in this process. The results revealed that AIII induced apoptosis through activating c-Jun N-terminal protein kinase (JNK) or extracellular signal related kinase (ERK) signaling pathway and generating NO. However, JNK or ERK inhibited autophagy, while NO had no effect on autophagy. Therefore, JNK, ERK or NO regulates two programmed death processes in different ways. AIII did not show obvious cytotoxic effect on human peripheral blood mononuclear cells, which indicated that AIII has less side effects on normal cells, and could be considered as a leading compound for developing novel anticancer drug.
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
Ye
Y
Wang
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
Lei
L
Xu
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.|Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
Li-Li
LL
Lou
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
Shao-Jiang
SJ
Song
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
Guo-Dong
GD
Yao
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
Meng-Yao
MY
Ge
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
Toshihiko
T
Hayashi
Kyoto Prefectural University of Medicine, Kyoto, 602-0866, Japan.
Shin-Ichi
SI
Tashiro
Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo, 194-8543, Japan.
Satoshi
S
Onodera
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China. ikejimat@vip.sina.com.
Takashi
T
Ikejima
D031403:Anemarrhena; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D027343:Rhizome; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D013256:Steroids / Q000302:isolation & purification / Q000494:pharmacology*
D010936:Plant Extracts; D012503:Saponins; D013256:Steroids; C543146:timosaponin AIII
Apoptosis; Autophagy; ERK; JNK; NO; Timosaponin AIII