Hansenia weberbaueriana (Fedde ex H.Wolff) Pimenov & Kljuykov Extract Suppresses Proliferation of HepG2 Cells via the PTEN-PI3K-AKT Pathway Uncovered by Integrating Network Pharmacology and Iin Vitro Experiments.

Yueqin Feng,Fengjin Hao

doi:10.3389/fphar.2021.620897

Yueqin Feng, Fengjin Hao

Open Access

https://doi.org/10.3389/fphar.2021.620897

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Abstract

Previous studies have shown that Hansenia weberbaueriana (Fedde ex H.Wolff) Pimenov & Kljuykov extracts (HWEs) have antitumor activity, but their mechanism in vitro is still unclear. In this study, we first combined network pharmacology with experimental evaluation and applied a comprehensive strategy to explore and prove the therapeutic potential and potential mechanism of HWE. The mRNA expression profiles of PTEN, PIK3A, and AKT1 are from the Cancer Cell Line Encyclopedia (CCLE) of the Broad Institute. Our results showed that HWE has a good inhibition on HepG2 cells, and a slight inhibition on other cells. The results of the CCLE database showed that PTEN/PIK3A/AKT1 mRNA expression was up-regulated in HepG2 cells. Through further study, it was found that HWE increased the release of LDH, induced early and late apoptosis, and increased ROS levels in HepG2 cells. Western blot showed that HWE regulates the expression of mitochondrial apoptosis-related proteins. Meanwhile, the expression of PTEN was increased, and the expression of phosphorylated PI3K and Akt was down-regulated after HWE treatment. Our results show that HWE promotes HepG2 cell apoptosis via the PTEN-PI3K-Akt signaling pathway. This study is the first to report the potential role of HWE in the treatment of liver cancer.

Highlights

Liver cancer is one of the major causes of cancer-related mortality all over the world, with hepatocellular carcinoma (HCC) accounts for 95% of liver cancers (Hartke et al, 2017)
Identification of Candidate Components in Hansenia weberbaueriana All phytochemicals of the H. weberbaueriana were retrieved from Traditional Chinese Medicine on Immuno-Oncology (TCMIO) database (Liu et al, 2020)
A total of 154 compounds were retrieved from Hansenia weberbaueriana, see Supplementary Material for details

Summary

Introduction

Liver cancer is one of the major causes of cancer-related mortality all over the world, with hepatocellular carcinoma (HCC) accounts for 95% of liver cancers (Hartke et al, 2017). Progressive HCC is rarely treated radically by surgery or in situ liver transplantation (Abou-Alfa et al, 2006), and traditional chemotherapeutic agents are multi-drug resistant and have a high incidence of toxic side effects, which seriously affects the quality of life of patients. This is essential for maintaining normal physiology, but the overall recurrence rate is 50–60% (Kudo 2011; Ang et al, 2015; Ma and Cheung, 2017), further research on the molecular mechanisms of HCC tumorigenesis is essential for coping with life-threatening HCC. Network pharmacology is a new and powerful tool that helps us understand the complex interactions between target proteins and small molecules from a biological perspective, similar to the holism concept of channel tropism in TCM (Wang et al, 2017)

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