Hypericin induces apoptosis in K562 cells via downregulation of Myc and Mdm2.

ABSTRACT

BACKGROUND: Nowadays, some studies have shown the effect of hypericin on cancer cells. However, considering the cytotoxicity of this plant and signs of anticancer activity in the plant, unfortunately, there is still no proper treatment for leukemia cancer cells. Therefore, the present study aims to evaluate the anticancer effect of hypericin in the treatment of leukemia cancer and its possible mechanism of action. METHODS: In this study, the K562 cell line was treated with different concentrations of hypericin for 24 and 48 h. Detection of cell death was performed by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide assay. The rate of cell apoptosis was measured by Annexin V/propidium iodide assay using flow cytometry. The expression of Bax, Bcl2, Myc, Mdm2, and P53 genes was evaluated by real-time polymerase chain reaction test, and immunocytochemistry (ICC) analysis was used for further evaluation of P53. RESULTS: The results showed that hypericin has a dose-dependent cytotoxic effect on the K562 (in much less dose compared with cisplatin). According to flow cytometry results, cell apoptosis after exposure to hypericin for 24 h was 53%, and ICC analysis on p53 confirmed this. Furthermore, after 24 h of exposure to hypericin with IC50 concentration, the expression of P53 and Bax genes increased and the expression of the Bcl2, Myc, and Mdm2 gene decreased. CONCLUSION: The results showed that hypericin exerts its cytotoxicity on K562 cancer cells by downregulating Mdm2 and Myc. Based on the data acquired from the present study and many investigations till now, hypericin can be a good option for leukemia cancer cells treatment.