Euxanthone Inhibits Hepatocellular Carcinoma Progression by Targeting the miR-199a-5p/E2F3 Regulatory Axis.

INTRODUCTION

Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths on a global scale. This study aimed to evaluate the effects of euxanthone on the proliferation 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 between 0 and 100 μM. Cell viability was evaluated 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, while a dual luciferase reporter assay validated the interaction between miR-199a-5p and E2F3.

RESULTS

Euxanthone significantly (P < 0.05) inhibited cell proliferation in all HCC cell lines, with IC50 values between 6.25 and 25 μM. HepG2 cells exhibited pronounced sensitivity, with an IC50 of 6.25 μM. Euxanthone induced a G1 phase arrest, characterized by decreased expression of Cyclin D1 and E, and increased levels of p21. Additionally, it upregulated miR-199a-5p, which was identified as a mediator of the antiproliferative effects by targeting E2F3. Euxanthone treatment also significantly (P < 0.05) inhibited HepG2 cell migration in a wound healing assay.

DISCUSSION: The findings demonstrate that euxanthone exerts its anticancer activity in HCC cells by modulating the miR-199a-5p/E2F3 axis, leading to G1 arrest and inhibition of migration. These results align with prior studies on natural compounds as modulators of oncogenic signaling pathways and highlight miR-199a-5p as a crucial mediator for anticancer effects of euxanthone. The low toxicity toward normal liver cells further emphasizes its therapeutic potential.

CONCLUSION

Taken together, 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, highlighting the need for further investigation into its clinical applications.