Molecular Mechanism of Synthesized Potential Anticancer Agent Chalcone in Leukemia Cell Line K562

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

(*) Corresponding Author


Chalcone, a precursor of flavonoids that are abundantly found in plants, has been investigated and found to possess anticancer activity. This study aimed to evaluate the effect of chalcone derivatives on the PI3K/AKT signaling pathway in the K562 cell line. A K562 cell line was treated with two chalcone derivatives: (E)-1-(4-aminophenyl)-3-(2,3dimethoxyphenyl)-prop-2-en-1-one (Compound 4), and (E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one) (Compound 7), and compared to the anticancer drugs imatinib and accutane. Measurement of AKT caspase-3, STAT3, and cyclin D1 were performed with ELISA, whilst cell cycle and apoptosis analysis were performed using flow cytometry. Both Compound 4 and Compound 7 at all concentrations showed the most significantly decreased AKT levels in K562. Compound 4 at 5 and 10 µg/mL, and Compound 7 at 10 µg/mL, significantly increased caspase-3 on K562, although this was lower than when using imatinib. Compound 4 and Compound 7 in all concentrations showed decreasing STAT3 on K562, which were comparable to imatinib. Compound 4 and Compound 7 showed the highest decrease of cyclin D1 among treatments, and also arrested  G0/G1 and G2/M phase in K562 cells, with the results being comparable to imatinib and Isotretinoin. Compound 4 and Compound 7 are promising anticancer agents that function via inhibition of the PI3K/AKT signaling pathway, induction of apoptosis through up-regulation of apoptotic markers, and blockade of cell cycle progression by regulating cell cycle-related factors.


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