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Enhanced Antiproliferation Potency of Electrical Pulse-Mediated Metformin and Cisplatin Combination Therapy on MDA-MB-231 Cells

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Abstract

We investigated the combined potency of metformin and cisplatin on the MDA-MB-231, triple-negative breast cancer (TNBC) cells with the application of electrical pulses. There are no targeted therapies for this subset of breast cancer because of the absence of specific biomarkers. Cytotoxic chemotherapy is the mainstream mode of treatment for TNBC, and cisplatin is the most commonly used chemotherapeutic drug. While there is a good response initially, TNBC cells develop drug resistance eventually. Thus, there is a need for alternate therapies. Toward this, we studied the antiproliferation characteristics of electrical pulse-mediated combination therapy using metformin, the commonly used Type-2 diabetes drug, along with cisplatin. We used metformin, as it has various anticancer properties caused by repressing energy pathways in a cancer cell. Application of 8 pulses of 1000 V/cm, 100 µs, at 1 Hz frequency, enhanced the drug uptake leading to cell viability as low as 25.86% at 30 µM cisplatin and 5 mM metformin in a 24 h study. Also, the same studies were conducted on MCF10A, a non-cancerous human epithelial cell. It aided in comparing the result for both MDA-MB-231 and MCF10A cell lines while establishing a better understanding of the experimental outcomes. Overall, the various experimental results from colony-forming assay, reactive oxidative analysis, and the intracellular glucose metabolic assay indicate the possibility of the electrical pulses-based cisplatin and metformin drug combination as a potential alternative to TNBC treatment.

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Acknowledgements

One of the authors (P Sahu) is extremely grateful to the Ross Fellowship and is also thankful to Dr. L. Mittal and Mr. P. Giri for their assistance, guidance in conducting the experiments, analyzing the results, and procuring supplies and samples. All the authors are grateful to the reviewers for their insightful comments.

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Authors and Affiliations

  1. School of Engineering Technology, Purdue University, West Lafayette, IN, USA

    Praveen Sahu & Raji Sundararajan

  2. Department of Biological Sciences, Purdue University, West Lafayette, IN, USA

    Ignacio G. Camarillo

  3. Purdue University Center for Cancer Research, West Lafayette, IN, USA

    Ignacio G. Camarillo

Authors
  1. Praveen Sahu
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  2. Ignacio G. Camarillo
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  3. Raji Sundararajan
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Contributions

Concept and design: R Sundararajan, P Sahu. Experiments: P Sahu, IG Camarillo, R Sundararajan. Data analysis and draft: P Sahu, R Sundararajan, IG Camarillo. Manuscript: all.

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Correspondence to Raji Sundararajan.

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Sahu, P., Camarillo, I.G. & Sundararajan, R. Enhanced Antiproliferation Potency of Electrical Pulse-Mediated Metformin and Cisplatin Combination Therapy on MDA-MB-231 Cells. Appl Biochem Biotechnol 194, 18–36 (2022). https://doi.org/10.1007/s12010-021-03723-5

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