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

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Rahnamay M., Mahdavi M., Shekarchi A., Zare P., Hosseinpour Feizi M.

2018

vol. 65

issue 3

397-402

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 μM) 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 μM, 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.

Inhibition of cell proliferation and induction of apoptosis in K562 human leukemia cells by the derivative (3-NpC) from dihydro-pyranochromenes family

100%

Rahimi R., Mahdavi M., Pejman S., Zare P., Balalaei S.

2015

vol. 62

issue 1

83-88

Leukemia is a particular type of cancer characterized by the failure of cell death or disability in differentiation of hematopoietic cells. Chronic myelogenus leukemia (CML) is the most studied kind of this cancer. In this study, anti-cancer effect of dihydro-pyranochromenes derivatives were investigated in the human leukemia K562 cells. These compounds were found to be active cell proliferation inhibitors using MTT assay. Among these compounds, 3-NpC was determined as stronger compound with IC50 value of 100±3.1 µM and was chosen for further studies. Induction of apoptosis was analyzed by AO/EtBr staining, DNA fragmentation assay, Annexin V/PI double staining and cell cycle analysis. Furthermore, Western Blot analysis showed that treatment of the cells with 3-NpC led to up-regulation and activation of caspase-3. The results of this investigation clearly indicated that dihydro-pyranochromenes derivatives induce apoptosis in the K562 cell line. This information signalizes also that these compounds may prepare a new therapeutic approach for the treatment of leukemia.

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2 Acta Biochimica Polonica

1 2018

1 2015

2 Mahdavi M.

2 Zare P.

1 Balalaei S.

1 Hosseinpour Feizi M.

1 Pejman S.

1 Rahimi R.

1 Rahnamay M.

1 Shekarchi A.

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

Inhibition of cell proliferation and induction of apoptosis in K562 human leukemia cells by the derivative (3-NpC) from dihydro-pyranochromenes family