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Synthesis of Pirano-Based Piranazole-based Compounds to Induce Apoptosis by Reducing the Expression of Anti-Apoptotic Protein B2 Cell Lymphoma Protein in the MCF-7 Human Breast Cancer Cell Category
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H Shahriyari-Nejad1    , N Pourmohsen1 , H Ghafouri 2, S Zareie1 , R Sharifi3 , N Mahmoodi3 |
1- Department of Biology, University of Guilan, Rasht, Iran
2- Department of Biology, University of Guilan, Rasht, Iran , h.ghafoori@guilan.ac.ir
3- Department of Chemistry, University of Guilan, Rasht, Iran |
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Abstract: (4443 Views) |
Background & aim: B-cell lymphoma 2 (Bcl-2) is a potential target for tumor treatment. The inhibition of the Bcl-2 production is research target of attraction in the field of anti-cancer drug development. The present study aimed to evaluate the inhibitory effects of novel pyrazole derivatives on Bcl-2 expression in human breast cancer cell line MCF-7.
Methods: In the present in vitro experimental study, the newly synthesized substances were screened against breast Aden carcinoma (MCF-7). The Western-blot analysis was carried out to study signaling pathways of MCF-7 breast cancer cells. The levels of apoptosis-related protein (Bcl-2) were evaluated by western blot analysis and changes in it expression were confirmed. Data were analyzed using one-way ANOVA, and independent t-test.
Results: The compounds HN1 and HN2 significantly inhibited the proliferation of human breast cancer cells. The compounds HN1and HN2 inhibited the growth of MCF-7 cells with IC50 values of 7.4 μg/ml and 8.68 μg/ml, respectively. In addition, compounds HN1and HN2 (22.5-50 μg/ml) significantly inhibited the anti-apoptotic Bcl-2 protein production. The compound HN2 significantly inhibited Bcl-2 expression in a concentration-dependent manner, corresponding 24% at 37.5 μg/ml, 30% at 50 μg/ml. Also compound HN1 at the same concentrations inhibited Bcl-2 expression by 12%, 0% at 50 and 37/5 μg/ml in MCF-7 cells, respectively.
Conclusion: HN2 could suppress the viability of MCF-7 cells and induce apoptosis in breast cancer cells by down-regulation of anti-apoptotic factor, Bcl-2. These results revealed that the potential inhibitory effect of HN2 against growth of MCF-7 human breast cancer cells might be associated with induction of apoptosis through Bcl-2 protein dependent pathway. The present results suggest that HN2 has a promising potential to be used as a valuable chemo preventive agent.
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| Keywords: Pyrazole, Apoptosis, MCF-7 cells, Bcl-2 |
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Full-Text [PDF 2076 kb]
(677 Downloads)
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Type of Study: Research |
Subject:
Biochemistry
Received: 2019/08/17 | Accepted: 2019/12/2 | Published: 2020/03/4
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