In vitro evaluation of newly developed chalcone analogues in human cancer cells

Purpose: Among flavonoids, chalcones have been identified as interesting co mpounds having chemopreventive and antitumor properties. We studied a panel of newly developed chalcone analogues (S1-S10) using MDA-MB 231 and MCF-7 ADRr breast cancer cells and the T-leukemic Jurkat cell line. Quercetin was used as the reference compound. Methods: Antiproliferative activity was ev aluated by cell counts performed after 72 h of exposure to the drugs. DNA a nalysis and redox activity were evaluated using flow cytometry. Apoptosis w as assessed by morphological analysis, using YOYO-1 as DNA dye; p-glycoprot ein function was ascertained by quantitating the efflux of rhodamine 123. R esults: All cells were sensitive to chalcone analogues yielding IC50 in mic romolar concentrations with the following order regardless of the multidrug resistance (MDR) status: S1 > S2 > quercetin. S1 and S2, the most active c ompounds, were selected to evaluate their effect on the cell cycle, apoptos is, redox activity, and modulation of the p-glycoprotein function. No signi ficant perturbation in cell cycle was seen with concentration up to 1 mu M after 24 h. After 72 h a slight increase in G(2)/M block and DNA fragmentat ion occurred at 10 mu M. Morphological analysis of apoptosis showed that ch alcone analogues: induced apoptosis to a higher extent than quercetin. Redo x analysis demonstrated that all substances were able to increase intracell ular thiol levels, which returned to baseline value after 24 h for all drug s except quercetin. Production of reactive oxygen species was essentially u naffected by all compounds. Finally, in MDR-positive MCF-7 ADRr cells chalc one analogues were unable to modulate p-glycoprotein function while quercet in was able to. Conclusions: Newly developed S1 and S2 chalcones have a dif ferent but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.