Anti-proliferative and apoptotic effects of the derivatives from 4-aryl-4H-chromene family on human leukemia K562 cells.

Previous studies suggest that 4-aryl-4H-chromenes are potent apoptosis-inducing agents in various cancer cell lines. In this study, anti-proliferative and apoptotic effects of the derivatives from 4-aryl-4H-chromene family were investigated in the human leukemia K562 cells using [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) growth inhibition assay. 3-NC was more active among these compounds with IC₅₀ of 65 nM and was selected for further studies. Apoptosis, as the mechanism of cell death, was investigated morphologically by Hoechst 33258 staining, cell surface expression assay of phosphatidylserine by Annexin V/PI technique, caspase-3 activation assay, as well as the formation of DNA ladder. The K562 cells underwent apoptosis upon a single dose (at IC₅₀ value) of the compound, and also increased caspase-3 activity by more than 2.3-fold, following a 72 h treatment. Caspase-9 was also activated which could be detected 48 hours post-treatment. Furthermore, Western blot analysis revealed that the treatment with the compound down-regulated the expression of certain IAP protein, including survivin. These data further suggest that these derivatives from 4-aryl-4H-chromene may provide a novel therapeutic approach for the treatment of leukemia.