Glycyrrhetinic acid and related compounds induce G1 arrest and apoptosis in human hepatocellular carcinoma HepG2.
Glycyrrhetinic acid (GA) and its related compounds are known to have anti-inflammatory activity and also to inhibit liver carcinogenesis and tumor growth. GA and related compounds inhibited cell proliferation of the human hepatoma cell line, HepG2. Among five compounds tested, ursolic acid and 18beta-olean-12-ene-3beta, 23, 28-triol (18beta-erythrotriol) were comparatively effective, where the 50% inhibitory dose was 20 microM and 25 microM, respectively. Flow-cytometric analysis showed that GA and the related compounds arrested the cell cycle in the G1-phase; in addition, GA-related compounds induced apoptosis at high dose. Western blot analysis indicated that the induction of apoptosis by GA and ursolic acid was accompanied with an activation of caspase-8 and a reduction in the anti-apoptotic proteins, Bcl-2 and Bcl-xL, although the pro-apoptotic proteins, Bax and Bak, remained unaffected. These results suggest that GA and its related compounds may be potent agents in liver cancer treatment.
Satomi
Yoshiko
Y
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. ysatomi@koto.kpu-m.ac.jp
Nishino
Hoyoku
H
Shibata
Shoji
S
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D017630:Connexins / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014315:Triterpenes / Q000494:pharmacology; D000097002:Gap Junction beta-1 Protein; D000097245:Ursolic Acid
D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D017630:Connexins; D006034:Glycyrrhetinic Acid; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D000097002:Gap Junction beta-1 Protein; D000097245:Ursolic Acid; C505530:CASP8 protein, human; C506433:CASP9 protein, human