Cytotoxic and apoptosis inducing effect of some pyrano [3, 2-c] pyridine derivatives against MCF-7 Breast Cancer Cells

  • Mohammad Rahnamay Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
  • Majid Mahdavi Department of Biology, University of Tabriz, Tabriz, Iran http://orcid.org/0000-0003-0041-0440
  • Ali Akbar Shekarchi Public Health Departments, Khalkhal Faculty of Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran.
  • Payman Zare Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
  • Mohammad Ali Hosseinpour Feizi Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran
Keywords: Apoptosis, Pyrano-pyridine, Breast Cancer, MCF-7 cells

Abstract

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 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 100 ±5.0, 180 ±6.0, 60 ±4.0 and 140 ±5.0 μM, respectively. 4-CP.P was determined as stronger 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, it was accompanied with 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.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 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 100 ±5.0, 180 ±6.0, 60 ±4.0 and 140 ±5.0 μM, respectively. 4-CP.P was determined as stronger 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, it was accompanied with 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.

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Published
2018-08-27
Section
Articles