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Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells.
Food Chem Toxicol. 2018 Jun; 116(Pt B):40-50.FC

Abstract

Juglone (JG), a naturally-occurring naphthoquinone of Manchurian walnut (Juglans mandshurica) was shown to inhibit proliferation in various tumor types. However, the molecular mechanisms of JG on the induction of apoptosis and autophagy in HepG2 cells have not been examined. Herein, we investigated that JG could inhibit cell proliferation by induction of G2/M phase arrest. Also, occurrence of apoptosis was closely related with loss of mitochondrial membrane potential, the changes of apoptosis-related proteins after treatment with JG. In addition, we found that JG caused autophagy, as evidenced by increased expressions of LC3-II and Beclin-1. Interestingly, inhibition of JG-induced autophagy by 3-methyladenine (3-MA) and wortmannin (WT) significantly decreased apoptosis, whereas the apoptosis inhibitor z-VAD-fmk slightly enhanced autophagy. Furthermore, the induction of autophagy and apoptosis was associated with activation of MAPK family members (p38 and JNK) and production of reactive oxygen species (ROS). Both JNK inhibitor (SP600125) and ROS scavenger (N-acetylcysteine, NAC) could attenuate JG-induced autophagy and apoptosis. However, the p38-specific inhibitor SB203580 enhanced autophagic and apoptotic death. Moreover, the ROS scavenger NAC prevented phosphorylation of both p38 and JNK. Collectively, our data revealed that JG induced G2/M phase arrest, apoptosis, and autophagy through the ROS-dependent signaling pathway.

Authors+Show Affiliations

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, China; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China.The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, China; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing 100083, China. Electronic address: yujie_fu@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29627502

Citation

Wang, Peng, et al. "Juglone Induces Apoptosis and Autophagy Via Modulation of Mitogen-activated Protein Kinase Pathways in Human Hepatocellular Carcinoma Cells." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 116, no. Pt B, 2018, pp. 40-50.
Wang P, Gao C, Wang W, et al. Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells. Food Chem Toxicol. 2018;116(Pt B):40-50.
Wang, P., Gao, C., Wang, W., Yao, L. P., Zhang, J., Zhang, S. D., Li, J., Fang, S. H., & Fu, Y. J. (2018). Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 116(Pt B), 40-50. https://doi.org/10.1016/j.fct.2018.04.004
Wang P, et al. Juglone Induces Apoptosis and Autophagy Via Modulation of Mitogen-activated Protein Kinase Pathways in Human Hepatocellular Carcinoma Cells. Food Chem Toxicol. 2018;116(Pt B):40-50. PubMed PMID: 29627502.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells. AU - Wang,Peng, AU - Gao,Chang, AU - Wang,Wei, AU - Yao,Li-Ping, AU - Zhang,Jing, AU - Zhang,Sun-Dong, AU - Li,Ji, AU - Fang,Shao-Hong, AU - Fu,Yu-Jie, Y1 - 2018/04/06/ PY - 2017/10/11/received PY - 2018/03/29/revised PY - 2018/04/03/accepted PY - 2018/4/9/pubmed PY - 2018/10/12/medline PY - 2018/4/9/entrez KW - Apoptosis KW - Autophagy KW - Human hepatocellular carcinoma cell KW - Juglone KW - MAPK KW - Reactive oxygen species SP - 40 EP - 50 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 116 IS - Pt B N2 - Juglone (JG), a naturally-occurring naphthoquinone of Manchurian walnut (Juglans mandshurica) was shown to inhibit proliferation in various tumor types. However, the molecular mechanisms of JG on the induction of apoptosis and autophagy in HepG2 cells have not been examined. Herein, we investigated that JG could inhibit cell proliferation by induction of G2/M phase arrest. Also, occurrence of apoptosis was closely related with loss of mitochondrial membrane potential, the changes of apoptosis-related proteins after treatment with JG. In addition, we found that JG caused autophagy, as evidenced by increased expressions of LC3-II and Beclin-1. Interestingly, inhibition of JG-induced autophagy by 3-methyladenine (3-MA) and wortmannin (WT) significantly decreased apoptosis, whereas the apoptosis inhibitor z-VAD-fmk slightly enhanced autophagy. Furthermore, the induction of autophagy and apoptosis was associated with activation of MAPK family members (p38 and JNK) and production of reactive oxygen species (ROS). Both JNK inhibitor (SP600125) and ROS scavenger (N-acetylcysteine, NAC) could attenuate JG-induced autophagy and apoptosis. However, the p38-specific inhibitor SB203580 enhanced autophagic and apoptotic death. Moreover, the ROS scavenger NAC prevented phosphorylation of both p38 and JNK. Collectively, our data revealed that JG induced G2/M phase arrest, apoptosis, and autophagy through the ROS-dependent signaling pathway. SN - 1873-6351 UR - https://www.unboundmedicine.com/medline/citation/29627502/Juglone_induces_apoptosis_and_autophagy_via_modulation_of_mitogen_activated_protein_kinase_pathways_in_human_hepatocellular_carcinoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(18)30206-0 DB - PRIME DP - Unbound Medicine ER -