Cytotoxic and apoptosis inducing effect of some pyrano [3, 2-c] pyridine derivatives against MCF-7 breast cancer cells

Anti-cancer activities of some pyrano-pyridines have been previously reported. Herein, we investigated anti-proliferative and apoptotic effects of the novel pyrano [3, 2-c] pyridine (P.P, TPM.P, 4-CP.P and 3-NP.P) compounds against MCF-7 breast cancer cells. The MCF-7 cells were cultured in the presence of various concentrations (20-200 pM) of the tested compounds for 3 days and the cell viability was determined by MTT assay. Induction of apoptosis was qualitatively assayed by acridine orange/ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, as well as quantitatively by Annexin V/PI double staining and cell cycle analysis. These compounds inhibited growth and proliferation of the MCF-7 cells in a dose- and time-dependent manner. The IC50 values of P.P, TPM.P, 4-CP.P and 3-NP.P after 24 h of exposure were calculated to be 100 +/- 5.0, 180 +/- 6.0, 60 +/- 4.0 and 140 +/- 5.0 mu M, respectively. 4-CP.P was determined as the most potent compound and was chosen for further studies. The result of flow cytometric cell cycle analysis indicated an increase in sub-G1 population after 72 h treatment of the cells. Furthermore, this was accompanied by exposure of phosphatidylserine (PS) in the outer cell membrane after time course of treatment with the 4-CP.P. Based on these observations, the pyrano [3, 2-c] pyridines can be regarded as a valuable candidate for further pharmaceutical evaluations.