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Chalcones are natural compounds described in the literature by its several properties including cytotoxic activity against several tumor types. Considering that the search for new chemotherapeutic agents is still necessary, the aim of this study was to investigate the cytotoxic mechanisms involved in cell death induced by a synthetic chalcone (A23) on different tumor cells. Chalcone A23 reduced the cell viability of twelve tumor cell lines in a concentration and time dependent manner and it was more cytotoxic against acute leukemia cells. Interestingly, the compound was non cytotoxic to normal cells and non-hemolytic to normal red blood cells. Chalcone A23 decreased the expression of cell proliferation marker KI-67 and blocked the G2/M phase in both K562 and Jurkat cell lines. Cells treated with A23 showed morphological features suggestive of apoptosis, the "latter pattern" in agarose gel, the externalization of phosphatidylserine and caspase-3 and PARP cleavage. Chalcone A23 significantly reduced the mitochondrial membrane potential, decreased the expression of anti-apoptotic proteins Bcl-2 and survivin and increased the expression of pro-apoptotic protein Bax, confirming the involvement of the intrinsic pathway. The increased mitochondrial permeability resulted in the release of AIF, cytochrome c and endonuclease G from the mitochondria to the cytosol. In addition, chalcone A23 increased the expression of FasR and induced Bid cleavage, showing the involvement of the extrinsic pathway. Finally, chalcone A23 seems to have a synergic effect with the chemotherapy drugs cytarabine and vincristine. These results suggest that A23 is an interesting compound with strong and selective anti-tumor activity.

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