Hypericin-mediated regulation of miR21 and miR34a and their target genes in MCF7 breast cancer cells

Abstract

Abstract Background: Hypericin is a polyphenolic compound derived from Hypericum perforatum that exhibits anticancer activity in various cancer cell types. The molecular mechanisms of hypericin action on breast cancer cells are unclear. We investigated the effects of hypericin on MCF7 human breast cancer cells and the potential role of miR21 and miR34a in mediating these effects. Methods and Results: We evaluated the cell viability of MCF7 cells exposed to different concentrations of hypericin for 24 and 48 hours by XTT assay. e treated MCF7 cells with 5 µg/mL concentration of hypericin for 24 hours. We then measured the expression levels of miR21, miR34a, and their target genes PTEN, BCL2, TP53, and CDK4 at both mRNA and protein levels by qRT-PCR and western blotting. Hypericin decreased the cell viability and increased the apoptosis rate of MCF7 cells in a dose- and time-dependent manner. Hypericin also modulated the expression levels of miR21 and miR34a in MCF7 cells. Hypericin upregulated the expression levels of PTEN and TP53 and downregulated the expression levels of BCL2 and CDK4 in MCF7 cells. The changes in gene expression were consistent with the changes in protein expression. Conclusion: Hypericin induces anticancer effects on MCF7 human breast cancer cells by reducing cell viability, inducing apoptosis, modulating miR21 and miR34a expression, and regulating PTEN, BCL2, TP53, and CDK4 expression. Our findings reveal novel molecular targets and pathways for hypericin action on breast cancer cells and suggest that hypericin may be a promising therapeutic agent for breast cancer treatment.