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Combination of furosemide, gold, and dopamine as a potential therapy for breast cancer

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Abstract

Breast cancer is one of the leading causes of death in women worldwide. Initially, it develops in the epithelium of the ducts or lobules of the breast glandular tissues with limited growth and the potential to metastasize. It is a highly heterogeneous malignancy; however, the common molecular mechanisms could help identify new targeted drugs for treating its subtypes. This study uses computational drug repositioning approaches to explore fresh drug candidates for breast cancer treatment. We also implemented reversal gene expression and gene expression–based signatures to explore novel drug candidates computationally. The drug activity profiles and related gene expression changes were acquired from the DrugBank, PubChem, and LINCS databases, and then in silico drug screening, molecular dynamics (MD) simulation, replica exchange MD simulations, and simulated annealing molecular dynamics (SAMD) simulations were conducted to discover and verify the valid drug candidates. We have found that compounds like furosemide, gold, and dopamine showed significant outcomes. Furthermore, the expression of genes related to breast cancer was observed to be reversed by these shortlisted drugs. Therefore, we postulate that combining furosemide, gold, and dopamine would be a potential combination therapy measurement for breast cancer patients.

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Data Availability

The datasets generated or analyzed during the current study are available from the primary author upon a reasonable request.

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Acknowledgements

The simulations in this work were supported by the Center for High-Performance Computing, Shanghai Jiao Tong University.

Funding

This study was supported by the National Natural Science Foundation of China (no: 31900528), Natural Science Foundation of Jiangsu Province (BK20190601), Research Project of Public Health Research Center of Jiangnan University (grant number: JUPH201822), and Youth Fund for Basic Research Project of Jiangnan University (grant number: JUSRP11953).

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Author notes

  1. Zhen Wang and Aamir Mehmood contributed equally to this work.

Authors and Affiliations

  1. Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China

    Zhen Wang, Jia Yao, Hui Zhang, Li Wang & Aman Chandra Kaushik

  2. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China

    Aamir Mehmood & Dong-Qing Wei

  3. Department of Biology, Faculty of Science, King Khalid University, Abha, Saudi Arabia

    Mohammed Al-Shehri

  4. Zhong**g Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Nanyang, Henan, China

    Dong-Qing Wei

  5. Peng Cheng Laboratory, Nanshan District, Shenzhen, Guangdong, China

    Dong-Qing Wei

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  1. Zhen Wang
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Contributions

A. C. K. designed the experiment. A. C. K., Z. W., and A. M. performed the entire computational experiments. A. C. K. and A. M. analyzed the data and wrote the manuscript. A. C. K., D. Q. W., Z. W., A. M., J. Y., H. Z., M. A-S., and L. W. read the manuscript and advised on method development. All authors have approved the final version of the manuscript.

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Correspondence to Aman Chandra Kaushik or Dong-Qing Wei.

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Wang, Z., Mehmood, A., Yao, J. et al. Combination of furosemide, gold, and dopamine as a potential therapy for breast cancer. Funct Integr Genomics 23, 94 (2023). https://doi.org/10.1007/s10142-023-01007-1

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