Achillea fragrantissima extract exerts its anticancer effect via induction of differentiation, cell cycle arrest and apoptosis in chronic myeloid leukemia (CML) cell line K562

Abstract

The advantages of herbs in cancer therapy/prevention are attributed to their broad inhibitory activity against multiple aberrant cancer specific pathways and non-toxic nature. Achillea fragrantissima (Af) is a traditional herb used to treat viral fever and chronic diseases such as arthritis and diabetes. However, the anticancer potential of Af has not been studied yet. Anticancer properties of extract from Af leaves were studied using human chronic myeloid leukemia (CML) (K562), T cell lymphoma (Jurkat) and hepatocellular carcinoma (HepG2) cell lines. Af extract induced morphological changes were studied using inverted light microscope and its effect on viability of cells was measured by trypan blue assay. Af extract altered the morphology of K562 and Jurkat cells from spherical to spindle shape. This shape change was considered indicative of initiation of differentiation and occurred at a low concentration of the extract (0.5 mg/ml) in K562 cells and at this concentration viability of K562 cells was not significantly affected. At higher (≥1 mg/ml) concentrations, Af extract induced elongation of K562 cells, which was considered indicative of cell cycle arrest. Increasing concentration of Af extract also caused plasma membrane rupture in a higher proportion of K562 cells resulting in reduced viability. Af extract reduced the viability of K562 cells in a time and dose dependent manner. Results from our study indicated Af extract as a potent inducer of differentiation, cell cycle arrest and apoptosis in K562 and Jurkat cells. Af extract activated these anticancer mechanisms in a concentration dependent manner. Anticancer activity of Af extract on K562 and Jurkat cells, mediated by multiple independent mechanisms, suggests its potential use in the treatment of drug resistant leukemia and other cancers. Key words: Chronic myeloid leukemia, chronic myeloid leukemia (CML), differentiation therapy, K562, Achillea fragrantissima, Jurkat, hepatocellular carcinoma (HepG2), cell cycle arrest, apoptosis.