Acute
leukemia is a disorder of the hematopoietic system characterized by the expansion of a clonal population of cells blocked from differentiating into mature cells. Recent studies have shown that
chalcones and their derivatives induce apoptosis in different cell lines. Since new compounds with
biological activity are needed, the aim of this study was to evaluate the cytotoxic effect of three synthetic
chalcones, derived from
1-naphthaldehyde and
2-naphthaldehyde, on human
acute myeloid leukemia K562 cells and on human
acute lymphoblastic leukemia Jurkat cells. Based on the results, the most cytotoxic compound (A1) was chosen for further analysis in six human acute
leukemia cells and in a human
colon adenocarcinoma cell line (HT-29).
Chalcone A1 significantly reduced the cell viability of K562, Jurkat, Kasumi, U937, CEM and NB4 cells in a concentration and time-dependent manner when compared with the control group (IC50 values between ∼1.5 μM and 40 μM). It was also cytotoxic to
HL-29 cells. To further examine its effect on normal cells, peripheral blood lymphocytes collected from healthy volunteers were incubated with the compound. It has also been incubated with human fibroblasts cultured from bone marrow (JMA).
Chalcone A1 is non-cytotoxic to PBL cells and to JMA cells. A1 caused significant cell cycle arrest in all phases according to the cell line, and increased the proportion of cells in the sub G0/G1 phase. To evaluate whether this
chalcone induced cell death via an apoptotic or necrotic pathway, cell morphology was examined using fluorescence microscopy. Cells treated with A1 at IC50 demonstrated the morphological characteristic of apoptosis, such as
chromatin condensation and formation of apoptotic bodies. Apoptosis was confirmed by externalization of
phosphatidylserine, which was detected by the
Annexin V-FITC method, and by DNA fragmentation. The results suggest that
chalcone A1 has potential as a new lead compound for
cancer therapy.