Impact of cataranthine treatment on miRNA34 and miRNA29 levels in HepG2 cells and their association with the expression levels of Bcl-2 and Nrf2.

Abstract

Introduction: Cataranthine is an alkaloid used in the development of anti-cancer drugs. In this study, the effect of cataranthine is assessed by measuring the levels of miR-34 and miRNA-29, which are effective regulators of BCL-2 and NRF-2 gene expression, and their relation to the survival of HCC cells.

Methods: This study used cataranthine, and the HepG2 cell line. The MTT test was used to determine the appropriate concentration of cataranthine for treatment (IC50). Oxidative stress status was assessed by evaluating TAC (total antioxidant capacity), TOS (total oxidant status), and MAD (malondialdehyde) levels. Flow cytometry was used to investigate apoptosis. The expression levels of Nrf2, Bcl2, miRNA34, and miRNA29 genes in HepG2 were evaluated by RT-PCR.

Results: We observed that cataranthine significantly reduced the levels of oxidative markers (MAD, and TOS) and, conversely, increased the level of antioxidant markers in HepG2 cells. Treatment of HepG2 cells with different doses of cataranthine significantly increased the expression of Nrf2 and Bcl-2 genes, while significantly decreasing the expression of miR29 and miR34 genes.

Conclusion: These findings suggest that cataranthine may exert its anticancer effects by reducing oxidative stress and promoting apoptosis, while decrease in miR34 and miR29 as well as increase in Nrf2 and Bcl2 may act as resistance mechanisms in cancer cells. The results highlight the dual potential of cataranthine in regulating cellular responses to oxidative stress and cell death in liver cancer, with dose-dependent modulatory effects.