2. Academic Validation
  3. Nitric oxide induces apoptosis and autophagy; autophagy down-regulates NO synthesis in physalin A-treated A375-S2 human melanoma cells

Nitric oxide induces apoptosis and autophagy; autophagy down-regulates NO synthesis in physalin A-treated A375-S2 human melanoma cells

  • Food Chem Toxicol. 2014 Sep;71:128-35. doi: 10.1016/j.fct.2014.06.007.
Hao He 1,  Yong-Sheng Feng 2,  Ling-He Zang 2,  Wei-Wei Liu 2,  Li-Qin Ding 3,  Li-Xia Chen 4,  Ning Kang 3,  Toshihiko Hayashi 2,  Shin-ichi Tashiro 5,  Satoshi Onodera 6,  Feng Qiu 7,  Takashi Ikejima 8
Affiliations

Affiliations

  • 1 Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People's Republic of China; China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People's Republic of China.
  • 2 China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People's Republic of China.
  • 3 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, People's Republic of China.
  • 4 Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People's Republic of China.
  • 5 Institute for Clinical and Biomedical Sciences, Kyoto 603-8072, Japan.
  • 6 Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo 194-8543, Japan.
  • 7 Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People's Republic of China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, People's Republic of China. Electronic address: fengqiu20070118@163.com.
  • 8 China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, People's Republic of China. Electronic address: ikejimat@vip.sina.com.
PMID: 24952311 DOI: 10.1016/j.fct.2014.06.007
Abstract

Physalin A is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has been used for the treatment of sore throat, hepatitis, eczema and tumors in China. Our previous study demonstrated that physalin A induced Apoptosis and cyto-protective Autophagy in A375-S2 human melanoma cells. Induction of Reactive Oxygen Species (ROS) with physalin A triggered Apoptosis. In this study, NO generated by physalin A induced Apoptosis and Autophagy in A375-S2 cells, since physalin A induced the expression of inducible nitric oxide synthase (iNOS) in the cells. Generation of NO partially promoted both Apoptosis and Autophagy in A375-S2 cells. NO suppressed mTOR expression, which led to Autophagy induction. An autophagic inhibitor, 3-methyladenine (3MA) promoted NO production, while acceleration of Autophagy with an autophagic agonist rapamycin repressed NO production, suggesting that Autophagy and NO production form a negative feedback loop that eventually protects the cells from Apoptosis. The results together with the previous study indicate Apoptosis and Autophagy induced by physalin A in A375-S2 cells; the Autophagy, repressing production of reactive nitrogen species (RNS) and ROS, protects the cells from Apoptosis.

Keywords

A375-S2 cells; Apoptosis; Autophagy; Nitric oxide; Physalin A; mTOR.

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