Inhibition of Cell Proliferation and Metastasis by Scutellarein Regulating PI3K/Akt/NF-κB Signaling through PTEN Activation in Hepatocellular Carcinoma.

Sang Eun Ha,Hun Hwan Kim,Ho Jeong Lee,Seong Min Kim,Preethi Vetrivel,Gon Sup Kim,Jeong Doo Heo,Pritam Bhagwan Bhosale

doi:10.3390/ijms22168841

Abstract

Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against several cancers. Human hepatocellular carcinoma (HCC) is major cancer type due to its poor prognosis even after treatment with chemotherapeutic drugs, which causes a variety of side effects in patients. Therefore, efforts have been made to develop effective biomarkers in the treatment of HCC in order to improve therapeutic outcomes using natural based agents. The current study used SCU as a treatment approach against HCC using the HepG2 cell line. Based on the cell viability assessment up to a 200 μM concentration of SCU, three low-toxic concentrations of (25, 50, and 100) μM were adopted for further investigation. SCU induced cell cycle arrest at the G2/M phase and inhibited cell migration and proliferation in HepG2 cells in a dose-dependent manner. Furthermore, increased PTEN expression by SCU led to the subsequent downregulation of PI3K/Akt/NF-κB signaling pathway related proteins. In addition, SCU regulated the metastasis with EMT and migration-related proteins in HepG2 cells. In summary, SCU inhibits cell proliferation and metastasis in HepG2 cells through PI3K/Akt/NF-κB signaling by upregulation of PTEN, suggesting that SCU might be used as a potential agent for HCC therapy.

Highlights

Liver cancer is a common malignant tumor and a leading cause of death worldwide
The results revealed that SCU significantly upregulated the protein expression of phosphatase and tensin homolog (PTEN), and the activity of SCU was higher than that of the PTEN inhibitor (Figure 4b)
Our findings indicate that SCU as a PTEN activator and may be usef5uolfin16 treatment option in hepatocellular carcinoma (HCC)

Summary

Introduction

Liver cancer is a common malignant tumor and a leading cause of death worldwide. According to the 2020 GLOBOCAN, approximately 905,677 new cases and an estimated 830,180 liver cancer-related deaths annually, making it the sixth leading cause of cancer death, occurred worldwide in 2020. About 90% of primary liver cancers are human hepatocellular carcinoma (HCC) [1]. Significant issues exist with the high rate of postsurgical recurrence and intrahepatic/extrahepatic metastases [2]. Current options for the treatment of HCC are chemotherapy, radiotherapy, and surgery, which largely depend upon the tumor size and stage of tumor severity. It is essential to find a complementary option with better efficacy and fewer side effects for HCC [3]

Methods

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Discussion

Conclusion