New 3-Cyano-2-Substituted Pyridines Induce Apoptosis in MCF 7 Breast Cancer Cells

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
A MalkiHayam M A Ashour

Abstract

The synthesis of new 3-cyano-2-substituted pyridines bearing various pharmacophores and functionalities at position 2 is described. The synthesized compounds were evaluated for their in vitro anti-cancer activities on five cancer cell lines using 5-FU as reference compound. The results revealed that the benzohydrazide derivative 9a induced growth inhibition in human breast cancer cell line MCF-7 with an IC50 value of 2 μM and it showed lower cytotoxicity on MCF-12a normal breast epithelial cells. Additionally, 9a induced apoptotic morphological changes and induced apoptosis in MCF-7 in a dose and time-dependent manner according to an enzyme linked immunosorbent apoptosis assay which is further confirmed by a TUNEL assay. Flow cytometric analysis indicated that 9a arrested MCF-7 cells in the G1 phase, which was further confirmed by increased expression of p21 and p27 and reduced expression of CDK2 and CDK4. Western blot data revealed significant upregulation of the expression of p53, Bax, caspase-3 and down-regulation of Bcl-2, Mdm-2 and Akt. Additionally, 9a increased the release of cytochrome c from mitochondria to cytoplasm which provokes the mitochondrial apoptotic pathway while it showed no significant change on the express...Continue Reading

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Citations

Jun 21, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yao WeiLimin Li
Feb 6, 2018·Oncology Letters·Shu-Jun ZhangBing-Lin Cheng
Jan 1, 2020·BMC Chemistry·Hassan M Abdel-AzizAbdullatif Bin Muhsinah
Oct 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rehab SabourNajla Altwaijry

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Methods Mentioned

BETA
ELISA
Flow Cytometric
flow cytometry
FCS
Assay
fluorescence microscopy
protein assay
electrophoresis

Software Mentioned

SPSS
Image J

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