Virtual screening and experimental analysis of caspase-7 inhibitors as candidates for extending the lifespan of CHO cells

IF 2.3 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Electronic Journal of Biotechnology Pub Date : 2024-06-13 DOI:10.1016/j.ejbt.2024.04.007
Sara Kafi , Sajad Najafi , Karim Mahnam , Shirin Farivar , Javad Ranjbari
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Abstract

Background

Chinese hamster ovarian (CHO) cells are widely employed in biotechnology for the production of recombinant proteins. Extending the life span of CHO cells and inhibiting the loss of producing cell population through the inhibition of apoptosis can benefit the productivity of those cells. In this study, we aimed to screen and evaluate the impact of some caspase-7 inhibitor candidates on the lifespan of CHO cells.

Results

Through virtual screening and molecular docking, risperidone was screened and selected as a potential inhibitor of caspase-7 in CHO cells. The results of MTT assay revealed that the cytotoxicity of risperidone at all concentrations was lower than 50%, and thus it can be suggested as a safe treatment for CHO cells. Annexin V apoptosis and flow cytometry assays revealed that risperidone at 1, 25, and 50 µM concentrations inhibited apoptosis 72 h post-treatment through caspase-7 inhibition. Although gene expression analysis through qRT-PCR demonstrates that risperidone did not affect caspase-7 gene expression.

Conclusions

This bioinformatics and experimental study suggests risperidone as a caspase-7 inhibitor with the potential to extend the lifespan of CHO cells and offers possible opportunities in biotechnology.

How to cite: Kafi S, Najafi S, Mahnam K, et al. Virtual screening and experimental analysis of caspase-7 inhibitors as candidates for extending the lifespan of CHO cells. Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.04.007.

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作为延长 CHO 细胞寿命候选物的 Caspase-7 抑制剂的虚拟筛选和实验分析
背景中国仓鼠卵巢(CHO)细胞在生物技术中被广泛用于生产重组蛋白质。通过抑制细胞凋亡来延长 CHO 细胞的寿命并抑制生产细胞数量的损失,有利于提高这些细胞的生产率。结果通过虚拟筛选和分子对接,筛选出利培酮(risperidone)作为CHO细胞中caspase-7的潜在抑制剂。MTT检测结果表明,利培酮在所有浓度下的细胞毒性均低于50%,因此可以作为一种安全的治疗CHO细胞的药物。Annexin V 细胞凋亡和流式细胞术检测显示,1、25 和 50 µM 浓度的利培酮可通过抑制 caspase-7 抑制处理后 72 小时的细胞凋亡。尽管通过 qRT-PCR 进行的基因表达分析表明利培酮并不影响 caspase-7 基因的表达。结论这项生物信息学和实验研究表明利培酮是一种 caspase-7 抑制剂,具有延长 CHO 细胞寿命的潜力,并为生物技术提供了可能的机遇:Kafi S, Najafi S, Mahnam K, et al. Virtual screening and experimental analysis of caspase-7 inhibitors as candidates for extending the lifespan of CHO cells.Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.04.007.
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来源期刊
Electronic Journal of Biotechnology
Electronic Journal of Biotechnology 工程技术-生物工程与应用微生物
CiteScore
5.60
自引率
0.00%
发文量
50
审稿时长
2 months
期刊介绍: Electronic Journal of Biotechnology is an international scientific electronic journal, which publishes papers from all areas related to Biotechnology. It covers from molecular biology and the chemistry of biological processes to aquatic and earth environmental aspects, computational applications, policy and ethical issues directly related to Biotechnology. The journal provides an effective way to publish research and review articles and short communications, video material, animation sequences and 3D are also accepted to support and enhance articles. The articles will be examined by a scientific committee and anonymous evaluators and published every two months in HTML and PDF formats (January 15th , March 15th, May 15th, July 15th, September 15th, November 15th). The following areas are covered in the Journal: • Animal Biotechnology • Biofilms • Bioinformatics • Biomedicine • Biopolicies of International Cooperation • Biosafety • Biotechnology Industry • Biotechnology of Human Disorders • Chemical Engineering • Environmental Biotechnology • Food Biotechnology • Marine Biotechnology • Microbial Biotechnology • Molecular Biology and Genetics •Nanobiotechnology • Omics • Plant Biotechnology • Process Biotechnology • Process Chemistry and Technology • Tissue Engineering
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