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Naringenin in combination with quercetin/fisetin shows synergistic anti-proliferative and migration reduction effects in breast cancer cell lines

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Abstract

Introduction & aim

Breast cancer is one of the most common cancers with a high mortality rate among women worldwide. Quercetin/fisetin and naringenin, three well-known flavonoids, have been used to fight against various cancers. The aim of the present study was to investigate the possible synergism of quercetin/fisetin with naringenin on MCF7 and MDA-MB-231 breast cancer cell lines.

Methods

In this study, cultured MCF7 and MDA-MB-231 cells were treated with different concentrations of quercetin/fisetin individually and in combination with naringenin. MTT assay and scratch assay was employed to determine cell viability and migration respectively. Real-time PCR was used to study the expression level of apoptosis genes and miR-1275 (tumor suppressor miRNA) and mir-27a-3p (oncogenic miRNA).

Results

A synergism effect of quercetin/fisetin and naringenin (CI < 1) was observed for both cell lines. Combination therapies were significantly more effective in cell growth reduction, migration suppression and apoptosis induction than single therapies. Gene expression analysis revealed the upregulation of miR-1275 and downregulation miR-27a-3p.

Conclusion

Our results indicate that quercetin/fisetin enhances the anti-proliferative and anti-migratory activities in combination with naringenin in MCF7 and MDA-MB-231 human breast cancer cell lines. Therefore, the combination of Que/Fis and Nar can be proposed as a promising therapeutic strategy for further investigations.

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Data availability

The data generated during and/or analyses during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran

    Masoume Jalalpour Choupanan, Shahrzad Shahbazi & Somayeh Reiisi

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  1. Masoume Jalalpour Choupanan
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  2. Shahrzad Shahbazi
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Contributions

M. Jalalpour Choupanan performed most of the experiments as part of his master’s degree in Genetics. Sh. Shahbazi performed miRNAs expression, and bioinformatics analysis and participated in intellectual discussions of the data. S.Reiisi coordinated the study, designed the experiments, and revised the manuscript.

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Correspondence to Somayeh Reiisi.

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Jalalpour Choupanan, M., Shahbazi, S. & Reiisi, S. Naringenin in combination with quercetin/fisetin shows synergistic anti-proliferative and migration reduction effects in breast cancer cell lines. Mol Biol Rep 50, 7489–7500 (2023). https://doi.org/10.1007/s11033-023-08664-2

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