The Combination Effect of Daphne Extract and Imatinib on the Antiproliferative Activity of the K562 Cell Line

Abstract

Background: Herbal medicine is well known among the ancient medical sciences. Healing properties have been observed in some species of Daphne. The effect of Daphne plant extract on the K562 cell line has been previously studied, and Gleevec is a well-known and effective drug for the treatment of chronic myelogenous leukemia. Material and Methods: In this study, the simultaneous effects of using herbal medicine and a targeted therapy drug on the K562 cell line were investigated. The presence of some species of Daphne in Iran motivated us to evaluate the cytotoxic effect of Daphne mucronata on human leukemia cancer cells. The antiproliferative activity of the dichloromethane extract of daphne mucronate (Thymelaeaceae), a new anticancer medicinal plant, was evaluated. Cell viability was quantitated by MTT assay. Apoptotic and necrotic changes in the cell membrane were examined using flow cytometry. Changes in Bax and Bcl2 gene expression were investigated using real-time PCR. The MIC and the IC50 of the crude extract were calculated, and the MIC and IC50 of the combination of the Daphne extract and imatinib were tested in the K-562 cell line. Results: K-562 cells responded to the extract treatments in a dose-dependent manner, and the increase in the expression of Bcl2 and decrease in the expression of the Bax gene increased with increasing extract concentration. Flow cytometry revealedthat most of the cells underwent apoptosis. Conclusion: Daphne extract effectively decreased the viability of the cell line. The necrotic effect of the Daphne extract was evaluated, and an increase in the gene expression of Bcl2 was observed in cells exposed to the Daphne extract. The combination of Daphne extracts with imatinib enhances the cytotoxic effect of imatinib.