Targeting Hepatocellular Carcinoma: Schisandrin A Triggers Mitochondrial Disruption and Ferroptosis

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lin-wei He, Chang-jie Lin, Lin-jun Zhuang, Yi-hui Sun, Ye-cheng Li, Zhen-yu Ye
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引用次数: 0

Abstract

The main focus of this research was to examine SchA's role in the hepatocellular carcinoma (HCC) development. LO2 and Huh7 cell viability were assessed using the MTT assay. The experiments included flow cytometry, colony formation, transwell, wound healing, and immunofluorescence assays to evaluate apoptosis levels, cells colony-forming ability, ROS levels, invasion and migration ability, and mitochondrial membrane potential. Biochemical kits was utilized for checking the ATP, mitochondrial DNA, MDA, GSH, and Fe2+ levels in the Huh7 cells, and western blot for measuring the ferroptosis and AMPK/mTOR related-protein expression levels. The MTT assay demonstrated that SchA significantly reduced the vitality of Huh7 cells ranging from 10 to 50 μM, whereas it exhibited no discernible impact on LO2 cells. Additionally, SchA significantly inhibited colony-forming ability, invasion ability, and migration ability within the concentration range of 10 to 50 μM, with a reduction of 68% in colony formation at 50 μM. SchA also induced apoptosis in a dose-dependent manner. Moreover, SchA was observed to significantly elevate ROS levels dose-dependently, down-regulate mitochondrial membrane potential (JC-1) at 20 and 50 μM, and reduce the levels of ATP and mtDNA dose-dependently. Various concentrations of SchA resulted in a notable elevation in MDA and Fe2+ levels as well as ACSL4 protein expression, accompanied by a reduction in GSH level and the protein expression of GPX4 and SLC7A11. Furthermore, SchA induced the activation of the AMPK/mTOR pathway in Huh7 cells, as evidenced by the increased phosphorylation level of AMPK and decreased phosphorylation level of mTOR. SchA might inhibit the progress of HCC through mitochondrial ferroptosis and dysfunction mediated by AMPK/mTOR pathway.

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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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