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ISL Induces Apoptosis and Autophagy in Hepatocellular Carcinoma via Downregulation of PI3K/AKT/mTOR Pathway in vivo and in vitro.


ABSTRACT: Aims:Isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, has previously been reported to have anti-tumor effects in vivo and in vitro. However, the mechanisms whereby ISL exerts its anticancer effects remain poorly understood in hepatocellular carcinoma (HCC). Purpose:In the present study, we investigated the anticancer efficacy and associated mechanisms of ISL in HCC MHCC97-H and SMMC7721 cells. Results:We found that ISL inhibited cell viability and proliferation and induced apoptosis in a dose- and time-dependent manner in liver cancer lines. Furthermore, ISL could activate autophagy in HCC cells, and the autophagy inhibitor HCQ enhances ISL-induced apoptosis in HCC cells. Additionally, ISL induced apoptosis and autophagy through inhibition of the PI3K/Akt/mTOR pathway. Most importantly, in a xenograft tumor model in nude mice, data showed that the administration of ISL decreased tumor growth and concurrently promoted the expression of LC3-II and cleaved-caspase-3. Interestingly, we found that ISL inhibits mTOR by docking onto the ATP-binding pocket of mTOR (ie, it competes with ATP). We thus suggest that mTOR is a potential target for ISL inhibition of hepatocellular carcinoma development, which could be of interest for future investigations. Conclusion:Taken together, the results reveal that ISL effectively inhibited proliferation and induced apoptosis in HCC through autophagy induction in vivo and in vitro, probably via the PI3K/Akt/mTOR pathway. ISL may be a potential therapeutic agent for hepatocellular carcinoma.

SUBMITTER: Song L 

PROVIDER: S-EPMC7585813 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ISL Induces Apoptosis and Autophagy in Hepatocellular Carcinoma via Downregulation of PI3K/AKT/mTOR Pathway in vivo and in vitro.

Song Lei L   Luo Yi Y   Li Shaoling S   Hong Ming M   Wang Qi Q   Chi Xiaoling X   Yang Cong C  

Drug design, development and therapy 20201020


<h4>Aims</h4>Isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, has previously been reported to have anti-tumor effects in vivo and in vitro. However, the mechanisms whereby ISL exerts its anticancer effects remain poorly understood in hepatocellular carcinoma (HCC).<h4>Purpose</h4>In the present study, we investigated the anticancer efficacy and associated mechanisms of ISL in HCC MHCC97-H and SMMC7721 cells.<h4>Results</h4>We found that ISL inhibited cell viability and proliferation  ...[more]

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