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Timosaponin AIII induces apoptosis and autophagy in human melanoma A375-S2 cells

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Abstract

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.

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Acknowledgments

Financial supported by National Natural Science Foundation of China (81373925) and Program for Liaoning Excellent Talents in University (LR2012034) are gratefully acknowledged.

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Authors and Affiliations

  1. China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People’s Republic of China

    Ye Wang, Lei Xu, Li-Li Lou, Guo-Dong Yao, Meng-Yao Ge, Toshihiko Hayashi & Takashi Ikejima

  2. Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Li-Li Lou & Shao-Jiang Song

  3. Kyoto Prefectural University of Medicine, Kyoto, 602-0866, Japan

    Shin-ichi Tashiro

  4. Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo, 194-8543, Japan

    Satoshi Onodera

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  1. Ye Wang
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  2. Lei Xu
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  3. Li-Li Lou
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  4. Shao-Jiang Song
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Correspondence to Takashi Ikejima.

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Wang, Y., Xu, L., Lou, LL. et al. Timosaponin AIII induces apoptosis and autophagy in human melanoma A375-S2 cells. Arch. Pharm. Res. 40, 69–78 (2017). https://doi.org/10.1007/s12272-016-0763-3

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  • DOI: https://doi.org/10.1007/s12272-016-0763-3

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