title: Apoptosis by aloe-emodin is mediated through down-regulation of calpain-2 and ubiquitin-protein ligase E3A in human hepatoma Huh-7 cells.
abstract: Natural flavonoids are associated with anti-proliferation of cancer growth. However, the antioxidant and anti-proliferation effects of AE (aloe-emodin) have not been well studied. We have investigated how AE affects the proliferation of hepatic hepatocellular carcinoma cells and exerts an anti-cancer effect. The cytotoxic effect of AE was demonstrated using an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and Huh-7 cells were inhibited by AE treatment in both dose- and time-dependent manners. The IC(50) level of AE was ∼75 μM. AE also has anti-proliferative effects via induction of DNA damage and apoptosis. 2-DE (two-dimensional electrophoresis) revealed that several proteins were related to the anti-cancer effects of AE. CAPN2 (calpain-2) and UBE3A (ubiquitin-protein ligase E3A), which are associated with the apoptosis signalling pathway, were verified by Western blotting. AE exhibited potent anti-proliferative effects on Huh-7 cells via down-regulation of CAPN2 and UBE3A. The findings support the possibility of AE being a chemopreventative agent.
authors.affiliation: Department of Biological Science, Gachon University of Medicine and Science, Yeonsugu, Incheon, Republic of Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Jeon
authors.forename: Young Keul
authors.initials: YK
authors.lastname: Jeon
authors.forename: Myeong Jin
authors.initials: MJ
authors.lastname: Nam
mesh_terms: D000504:Aloe / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004642:Emodin / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044767:Ubiquitin-Protein Ligases; D002154:Calpain; C569870:CAPN2 protein, human; D004642:Emodin