Natural Cyclopeptide RA-XII, a New Autophagy Inhibitor, Suppresses Protective Autophagy for Enhancing Apoptosis through AMPK/mTOR/P70S6K Pathways in HepG2 Cells
Song, Lihua1; Wang, Zhe1; Wang, Yurong1; Guo, Di1; Yang, Jianhong2,3; Chen, Lijuan2,3; Tan, Ninghua1,4
2017-11-01
发表期刊MOLECULES
ISSN1420-3049
卷号22期号:11页码:UNSP 1934
摘要Liver cancer is a progressive, irreversible and aggressive malignant disease, which has no effective chemotherapeutic drugs. RA-XII, a natural cyclopeptide isolated from the traditional Chinese medicine Rubia yunnanensis, exerts anti-cancer and anti-inflammatory activities. This work aimed to investigate the effects of RA-XII on a hepatic tumor and its underlying mechanisms in human hepatoma HepG2 cells. The results showed that RA-XII effectively inhibited the proliferation of HepG2 cells. Consistently, RA-XII significantly induced apoptosis in HepG2 cells by decreasing the expression of caspase 3, 8, 9, and promoting the Cleavage of PARP. Moreover, RA-XII-induced apoptosis was attenuated in the presence of apoptosis inhibitor N-Benzyloxycarbonyl-Val-Ala-Asp (O-Me) fluoromethyl keton, suggesting that RA-XII induced apoptosis-cell-death in HepG2 cells. Furthermore, autophagy-related proteins and mRNA levels were dramatically reduced after RA-XII treatment. Meanwhile, we observed that autophagy inhibitor chloroquine could enhance apoptosis in RA-XII-treated HepG2 cells, indicating that autophagy played a protective role in HepG2 cells and RA-XII might inhibit protective autophagy. Further analysis showed that RA-XII inhibited AMPK phosphorylation and led to the mTOR/P70S6K pathway activation, suggesting that RA-XII inhibited autophagy through AMPK/mTOR/P70S6K pathways. This study demonstrated that RA-XII promoted apoptosis and inhibited protective autophagy through AMPK/mTOR/P70S6K pathways in HepG2 cells. In conclusion, these findings suggest that RA-XII might potentially be a candidate as an autophagy inhibitor agent for further therapy of liver cancer.
关键词Ra-xii Cyclopeptide Autophagy Apoptosis Mtor Hepg2 Liver Cancer Cells
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/60482
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.China Pharmaceut Univ, Sch Tradit Chinese Pharm, 639 Longmian Ave, Nanjing 211198, Jiangsu, Peoples R China
2.Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China
3.Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
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Song, Lihua,Wang, Zhe,Wang, Yurong,et al. Natural Cyclopeptide RA-XII, a New Autophagy Inhibitor, Suppresses Protective Autophagy for Enhancing Apoptosis through AMPK/mTOR/P70S6K Pathways in HepG2 Cells[J]. MOLECULES,2017,22(11):UNSP 1934.
APA Song, Lihua.,Wang, Zhe.,Wang, Yurong.,Guo, Di.,Yang, Jianhong.,...&Tan, Ninghua.(2017).Natural Cyclopeptide RA-XII, a New Autophagy Inhibitor, Suppresses Protective Autophagy for Enhancing Apoptosis through AMPK/mTOR/P70S6K Pathways in HepG2 Cells.MOLECULES,22(11),UNSP 1934.
MLA Song, Lihua,et al."Natural Cyclopeptide RA-XII, a New Autophagy Inhibitor, Suppresses Protective Autophagy for Enhancing Apoptosis through AMPK/mTOR/P70S6K Pathways in HepG2 Cells".MOLECULES 22.11(2017):UNSP 1934.
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