Isorhamnetin Inhibits the Proliferation and Induces Apoptosis of Hepatocellular Carcinoma by Targeting the GSK3-β/PI3K/AKT Pathway

Liu S, Lin Y, Li H, He X, Zhang C, Lan S, Yao X, Guo W and Chen H

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine. China
Department of Pathology, The First Affiliated Hospital of Sun Yat Sen University, China
The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, China
Shenzhen TCM Anorectal Hospital (Futian), China
These authors contributed equally to this work

^*Correspondance to: Wei Guo 

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Abstract:

The natural compound possesses quality therapeutic effects and few side effects, development of new uses for marketed drugs, is an effective way to discover new antitumor compounds. Here, we have investigated the mechanism of Isorhamnetin (ISO) in the prevention and treatment of Hepatocellular Carcinoma (HCC). In-vitro cell models were used to measure the regulation effects of ISO on HCC, CCK-8 proliferation assay, wound healing assay and Transwell invasive assay were used to choose the of candidate cell lines. Flow cytometric analysis of apoptosis, and Western blot were performed to elucidate the mechanism of ISO. The targets on HCC was predicted using network pharmacology and molecular docking analyses. The putative pathways were further verified in vivo assays. The vitro experiments were demonstrated that ISO potently suppressed the proliferation, colony formations, wound healing well as invasive process in HCC. Network and biological analyses predicted that one of the core mechanisms about ISO on HCC was via regulation of cancer cell apoptosis, western blotting validated ISO inhibited HCC via GSK-β/PI3K/AKT pathway. Also, in mouse hepatocellular carcinoma xenograft model, ISO inhibited tumor growth with few side effects. These findings suggest that ISO is the natural anti-cancer compounds to inhibitor HCC effectively through the GSK-β/PI3K/AKT signaling pathway. Natural anti-cancer therapy maybe a promising strategy for the prevention and treatment of HCC.

Keywords:

Isorhamnetin; Network pharmacology; Molecule docking; Hepatocellular carcinoma; GSK-β/PI3K/AKT signaling pathway

Cite the Article:

Liu S, Lin Y, Li H, He X, Zhang C, Lan S, et al. Isorhamnetin Inhibits the Proliferation and Induces Apoptosis of Hepatocellular Carcinoma by Targeting the GSK3-β/PI3K/AKT Pathway. Clin Oncol. 2024;9:2052..