Inhibition of growth and induction of differentiation and apoptosis in human leukemia K562 cells by a new compound from dihydropyrano[c]chromenes family

Abstract

Aim: It has been reported that derivatives from the chromene family have potent anti-leukemic activity. Differentiation therapy is a promising treatment for myeloid leukemia. Herein, we evaluated inhibition of growth, differentiation induction and apoptosis in human myeloid leukemia K562 cells by the novel derivatives of dihydropyrano[c]chromenes. Methods: K562 cells were treated with different concentrations of the new dihydropyrano[c]chromenes (20-260 μM) derivatives for 3 days. To investigate growth inhibition and viability of the cells, a trypan blue exclusion assay was applied. Differentiation was investigated morphologically by wright-Giemsa staining and latex particle phagocytosis assay. Apoptosis was observed by morphological criteria, the acridine orange/ethidium bromide (AO/EtBr) double staining method, as well as DNA ladder formation. Results: The IC50 values of the 4-PC, 4-NC, 4-CNC and 4-HC after 48 h of exposure was 240±4.5, 60±3.5, 180±4.2 and 160±5.5 μM for K562 cells, respectively. 4-NC was found to be the most effective compound and was chosen for further studies. 4-NC inhibited growth and proliferation in a dose- and time-dependent manner. Moreover, our evidence showed that the 4-NC effects on K562 cells resulted in differentiation toward a monocyte/macrophage lineage. The data from the AO/EtBr and DNA fragmentation assay confirmed qualitatively that K562 cell treatment with 4-NC induces apoptosis. Conclusion: Based on our current observations, these compounds can be valuable candidates for effective chemotherapy acting through differentiation induction and apoptosis.