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n-3 PUFAs synergistically enhance the efficacy of doxorubicin by inhibiting the proliferation and invasion of breast cancer cells

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Abstract

Breast cancer stands as a prominent contributor to cancer-related fatalities among women globally, characterized by an unfavorable prognosis, low survival rates, and its conventional treatment approach involving chemotherapy. Doxorubicin (DOXO) represents a potent anti-tumor agent widely employed in combating breast cancer. Regrettably, a substantial proportion of patients eventually develop resistance to DOXO treatment, elevating the risk of relapse and adverse clinical outcomes. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), recognized as essential components of the human diet, have exhibited considerable promise in targeting malignant cells, initiating apoptosis, and impeding tumor proliferation and metastatic dissemination. Combining these nutritional supplements, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with DOXO presents a compelling strategy to augment treatment efficacy. The present study was conducted employing a breast cancer cell line, MCF-7, to assess the synergistic potential of DHA, EPA, and DOXO. Remarkably, the combination treatment yielded a substantial increase in cytotoxicity compared to the administration of DOXO alone. Furthermore, an enhancement in the suppression of metastasis was evident in the combination treatment relative to the exclusive use of DOXO. Cell cycle analysis unveiled that cells subjected to the combination treatment exhibited a more pronounced arrest in the G1 phase, signifying the combination’s heightened effectiveness in impeding cell progression into the doubling phase. Collectively, the amalgamation of n-3 polyunsaturated fatty acids (n-3 PUFAs) emerges as a potent strategy for enhancing the therapeutic potential of DOXO, effectively restraining the growth and dissemination of breast cancer cells.

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Data are available on request from the authors.

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Acknowledgements

The authors would like to thank the Director, MIT School of Bioengineering Sciences & Research, MIT ADT University, for infrastructure support and funding. We also thank Atal Incubation Centre, MIT ADT University, for providing access to the flow cytometer.

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MIT School of Bioengineering Sciences & Research, MIT ADT University, Pune, India.

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PG designed the study, carried out the investigation, data analysis, and wrote the original draft. TP contributed in the methodology of Figs. 1 and 2. SH contributed in the methodology of Figs. 1 and 3. KRN contributed in the conceptualisation, project administration, funding acquisition, and writing—review & editing of manuscript.

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Correspondence to R. N. Kedar.

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Gurav, P., Patade, T., Hajare, S. et al. n-3 PUFAs synergistically enhance the efficacy of doxorubicin by inhibiting the proliferation and invasion of breast cancer cells. Med Oncol 41, 2 (2024). https://doi.org/10.1007/s12032-023-02229-w

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