Engglis

Abstract

Two chalcone derivatives i.e. (E)-1-(4-aminophenyl)-3-(2,3dimethoxyphenyl)-prop-2-en-1- one (Compound-1), and (E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one) (Compound-2), has been proven to have potential cytotoxic activity. The aim of this study was to evaluate the effect of these compounds on PI3K/Akt signalling pathway in K562 cell lines. After incubation with the tested compounds, AKT, caspase-3, STAT3 and cyclin D1 concentrations were measured using ELISA. Furthermore, cell cycle was analysed using flowcytometry. Imatinib and isotretinoin were used as positive control, whereas cell culture without treatment was used as negative control. The AKT concentration after treatment with Compound-1 and -2 was significantly lower than that control, imatinib and isotretinoin (p<0.05). The apoptotic indices after treatment with Compound-1 and -2 were significantly higher than control, however they were lower than imatinib and isotretinoin (p<0.05). The caspase-3 concentration after treatment with Compound-1 at 5 and 10 μg/mL and Compound-2 at 10 μg/mL was significantly higher than that control and imatinib, however it was lower than isotretinoin (p<0.05). The STAT3 concentration after treatment with Compound-1 and -2 was significantly lower than that control and isotretinoin at 50 μg/mL (p<0.05) and similar with imatinib (p>0.05). The cyclin D1 concentration after treatment with Compound-1 and -2 was significantly lower than that control, imatinib and isotretinoin (p<0.05). In addition, Compound-1 and -2 arrested G0/ G1 and G2/M phase in K562 cell lines, with comparable results to imatinib and isotretinoin. In conclusion, the mechanism of cytotoxic activity of Compound-1 and -2 are through the PI3K/Akt signalling pathway inhibition, apoptosis induction by upregulation of apoptotic markers, and inhibition of cell cycle progression by regulating cell cycle-related factors.