التفاصيل البيبلوغرافية
| العنوان: |
Hellebrigenin induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells through inhibition of Akt. |
| المؤلفون: |
Deng, Li-Juan1, Hu, Li-Ping1, Peng, Qun-Long1, Yang, Xiao-Lin1, Bai, Liang-Liang1, Yiu, Anita2, Li, Yong1, Tian, Hai-Yan1, Ye, Wen-Cai1 chyewc@gmail.com, Zhang, Dong-Mei1 dmzhang701@foxmail.com |
| المصدر: |
Chemico-Biological Interactions. Aug2014, Vol. 219, p184-194. 11p. |
| مصطلحات موضوعية: |
*BUFADIENOLIDES, *CANCER cells, *DNA damage, *CELL cycle, *CYCLINS, *APOPTOSIS, *CYTOCHROME c, *ADP-ribosyltransferases |
| مستخلص: |
Hellebrigenin, one of bufadienolides belonging to cardioactive steroids, was found in skin secretions of toads and plants of Helleborus and Kalanchoe genera. In searching for natural constituents with anti-hepatoma activities, we found that hellebrigenin, isolated from traditional Chinese medicine Venenum Bufonis, potently reduced the viability and colony formation of human hepatocellular carcinoma cells HepG2, and went on to explore the underlying molecular mechanisms. Our results demonstrated that hellebrigenin triggered DNA damage through DNA double-stranded breaks and subsequently induced cell cycle G 2 /M arrest associated with up-regulation of p-ATM (Ser 1981 ), p-Chk2 (Tyr 68 ), p-CDK1 (Tyr 15 ) and Cyclin B1, and down-regulation of p-CDC25C (Ser 216 ). It was also found that hellebrigenin induced mitochondrial apoptosis, characterized by Bax translocation to mitochondria, disruption of mitochondrial membrane potential, release of cytochrome c into cytosol and sequential activation of caspases and PARP. In addition, Akt expression and phosphorylation were inhibited by hellebrigenin, whereas Akt silencing with siRNA significantly blocked cell cycle arrest but enhanced apoptosis induced by hellebrigenin. Activation of Akt by human insulin-like growth factor I (hIGF-I) could obviously attenuate hellebrigenin-induced cell death. In summary, our study is the first to report the efficacy of hellebrigenin against HepG2 and elucidated its molecular mechanisms including DNA damage, mitochondria collapse, cell cycle arrest and apoptosis, which will contribute to the development of hellebrigenin into a chemotherapeutic agent in the treatment of liver cancer. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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