期刊
ONCOTARGET
卷 7, 期 23, 页码 33948-33959出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8608
关键词
ergosterol peroxide; pAKT; c-Myc; Foxo3; puma
资金
- National Key Technology R D Program [2013BAD16B05]
- Guangdong Key Technology Program [2012A020100010]
- Introduction of Leading Talent Project of Guangdong Academy of Sciences [GD2015T001]
- Natural Sciences and Engineering Research Council of Canada (NSERC) [227937-2012]
- Heart and Stroke Foundation of Ontario [CI 7418]
Sterols are the important active ingredients of fungal secondary metabolites to induce death of tumor cells. In our previous study, we found that ergosterol peroxide (5a, 8a-epidioxiergosta-6, 22-dien-3 beta-ol), purified from Ganoderma lucidum, induced human cancer cell death. Since the amount of purified ergosterol peroxide is not sufficient to perform in vivo experiments or apply clinically, we developed an approach to synthesize ergosterol peroxide chemically. After confirming the production of ergosterol peroxide, we examined the biological functions of the synthetic ergosterol peroxide. The results showed that ergosterol peroxide induced cell death and inhibited cell migration, cell cycle progression, and colony growth of human hepatocellular carcinoma cells. We further examined the mechanism associated with this effect and found that treatment with ergosterol peroxide increased the expression of Foxo3 mRNA and protein in HepG2 cells. The upstream signal proteins pAKT and c-Myc, which can inhibit Foxo3 functions, were clearly decreased in HepG2 cells treated with ergosterol peroxide. The levels of Puma and Bax, pro-apoptotic proteins, were effectively enhanced. Our results suggest that ergosterol peroxide stimulated Foxo3 activity by inhibiting pAKT and c-Myc and activating pro-apoptotic protein Puma and Bax to induce cancer cell death.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据