Mechanism of cytotoxic activity of chalcone derivatives against K562 leukemia cell lines

Arina Novilla(1*), . Mustofa(2), Indwiani Astuti(3), . Jumina(4), Hery Suwito(5)

(1) Doctoral Program of Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Department of Medical Laboratory Technology, School of Health Sciences Jenderal Achmad Yani, Cimahi
(2) Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta
(3) Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta
(5) Department of Biology, Faculty of Science and Technology, Airlangga University, Surabaya, Indonesia
(*) Corresponding Author


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.


anticancer - chalcone derivatives – leukemia – K562 cell line - PI3K/Akt signaling

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