ArticleMolecules (Basel, Switzerland)2016
New 3-Cyano-2-Substituted Pyridines Induce Apoptosis in MCF 7 Breast Cancer Cells.
Article in Molecules (Basel, Switzerland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 38 citations in OpenAlex.
- Nicotinonitriles-based therapeutics as versatile pharmacophores in rational anticancer drug design.RSC advances · 2026Review
- Synthesis, biological evaluation and molecular docking of new triphenylamine-linked pyridine, thiazole and pyrazole analogues as anticancer agents.BMC chemistry · 2022Article
- Pathogenesis and Diagnostic Significance of EBV-miR-BARTs in Nasopharyngeal Carcinoma.Oxidative medicine and cellular longevity · 2022Article
- New pyridine and chromene scaffolds as potent vasorelaxant and anticancer agents.RSC advances · 2021Article
- Discovery of Novel 3-Cyanopyridines as Survivin Modulators and Apoptosis Inducers.Molecules (Basel, Switzerland) · 2020Article
- Preparation andRSC advances · 2019Article
- Facile synthesis and antiproliferative activity of new 3-cyanopyridines.BMC chemistry · 2019Article
- 5-Fluorouracil-induced mitochondrial oxidative cytotoxicity and apoptosis are increased in MCF-7 human breast cancer cells by TRPV1 channel activation but not Hypericum perforatum treatment.Molecular and cellular biochemistry · 2018Article
- Role of piwi-interacting RNA-651 in the carcinogenesis of non-small cell lung cancer.Oncology letters · 2018Article
- Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes.Molecules (Basel, Switzerland) · 2016Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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 expression of the death receptor proteins procaspase-8, caspase-8 and FAS. Furthermore, 9a reduced the expression of phospho AKT and β-catenin in dose dependent manner while inhibiting the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). Our findings suggest that compound 9a could be considered as a lead structure for further development of more potent apoptosis inducing agents with anti-metastatic activities.
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