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Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells.
Yang, J; Sun, Y; Xu, F; Liu, W; Hayashi, T; Mizuno, K; Hattori, S; Fujisaki, H; Ikejima, T.
Afiliación
  • Yang J; Department of Pharmacy, 159411The Third People's Hospital of Chengdu, Chengdu, Sichuan, People's Republic of China.
  • Sun Y; Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
  • Xu F; Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
  • Liu W; Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
  • Hayashi T; Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
  • Mizuno K; Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
  • Hattori S; Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, Hachioji, Tokyo, Japan.
  • Fujisaki H; Nippi Research Institute of Biomatrix, Toride, Ibaraki, Japan.
  • Ikejima T; Nippi Research Institute of Biomatrix, Toride, Ibaraki, Japan.
Hum Exp Toxicol ; 40(12): 2048-2062, 2021 Dec.
Article en En | MEDLINE | ID: mdl-34053323
PURPOSE: The mechanism of cytotoxicity of silibinin on two human hepatocellular carcinoma (HCC) cell lines, HepG2 (p53 wild-type) and Hep3B cells (p53 null), is examined in relation with the induction of autophagy and phosphorylation of AMP-activated protein kinase (p-AMPK). MATERIALS AND METHODS: Levels of apoptosis in relation to the levels of autophagy and those of glycolysis-related proteins, glucose transporter 1/4 (Glut1/4) and hexokinase-II (HK2), in HepG2 and Hep3B cells were examined. RESULTS: Silibinin-induced apoptosis was incomplete for HCC cell death in that up-regulated autophagy and/or reduced level of glycolysis, which are induced by silibinin treatment, antagonized silibinin-induced apoptosis. Inhibition of autophagy with 3-methyl adenine (3MA) or blocking of AMP-activated protein kinase (AMPK) activation with Compound C (CC) enhanced silibinin-induced apoptosis. The results confirm that AMPK involved in autophagy as well as in glycolysis remaining with silibinin is responsible for attenuation of silibinin-induced apoptosis. Blocking of AMPK or autophagy contributes to the enhancement of silibinin's cytotoxicity to HepG2 and Hep3B cells. CONCLUSION: This study shows that incomplete apoptosis of HCC by silibinin treatment becomes complete by repression of autophagy and/or glycolysis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Silimarina / Carcinoma Hepatocelular / Neoplasias Hepáticas / Antineoplásicos Fitogénicos Límite: Humans Idioma: En Revista: Hum Exp Toxicol Asunto de la revista: TOXICOLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Silimarina / Carcinoma Hepatocelular / Neoplasias Hepáticas / Antineoplásicos Fitogénicos Límite: Humans Idioma: En Revista: Hum Exp Toxicol Asunto de la revista: TOXICOLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido