Title : Euxanthone suppresses the proliferation of human hepatocellular carcinoma cells via miR-199a-5p/E2F3 axis
Abstract:
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. This study aimed to evaluate the effects of euxanthone on the proliferation and migration of HCC cell lines and elucidate the underlying molecular mechanisms.
Methods: HCC cell lines (HepG2, Huh-7, SNU-398, SK-HEP-1, Hep3B) and the normal liver cell line THLE-2 were cultured and treated with euxanthone at concentrations ranging from 0 to 100 µM. Cell viability was assessed using the MTT assay, while phase contrast microscopy and cell cycle analysis were performed to evaluate morphological changes and cell cycle distribution. qRT-PCR was utilized to measure miRNA and mRNA expression levels, and a dual luciferase reporter assay was conducted to confirm the interaction between miR-199a-5p and E2F3.
Results: Euxanthone significantly inhibited cell proliferation in all HCC cell lines, with IC?? values ranging from 6.25 to 25 µM. HepG2 cells showed pronounced sensitivity, with IC?? at 6.25 µM. Euxanthone induced G1 phase arrest, marked by decreased Cyclin D1 and E expression and increased p21 levels. Additionally, it upregulated miR-199a-5p, which was identified as a mediator of the antiproliferative effects by targeting E2F3. Euxanthone treatment also significantly inhibited HepG2 cell migration in a wound healing assay.
Conclusion: Euxanthone exerts antiproliferative effects on HCC cells via the miR-199a-5p/E2F3 axis and inhibits cell migration. These findings support its potential as a therapeutic agent for HCC, warranting further investigation into its clinical applications.
Keywords: Hepatocellular carcinoma, Euxanthone, MicroRNA-199a-5p, E2F3, Cell cycle arrest.
