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Eprinomectin: a derivative of ivermectin suppresses growth and metastatic phenotypes of prostate cancer cells by targeting the β-catenin signaling pathway

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Abstract

Purpose

Prostate cancer (PCa) is the second leading cause of cancer death among men in the USA. The emergence of resistance to androgen deprivation therapy gives rise to metastatic castration-resistant prostate cancer. Eprinomectin (EP) is a member of a family of drugs called avermectins with parasiticide and anticancer properties. The pupose of this study was to evaluate the anticancer effects of EP against metastatic PCa using cellular models. 

Methods

In this study, we have investigated the effect of EP’s anticancer properties and delineated the underlying mechanisms in the DU145 cellular model using several assays such as cell viability assay, colony formation assay, wound-healing assay, immunofluorescence, apoptosis assay, cell cycle analysis, and immunoblotting.

Results

Our results indicate that EP significantly inhibits the cell viability, colony formation, and migration capacities of DU145 cells. EP induces cell cycle arrest at the G0/G1 phase, apoptosis via the activation of different caspases, and autophagy through the increase in the generation of reactive oxygen species and endoplasmic reticulum stress. In addition, EP downregulates the expression of cancer stem cell markers and mediates the translocation of β-catenin from the nucleus to the cytoplasm, indicating its role in inhibiting downstream target genes such as c-Myc and cyclin D1.

Conclusion

Our study shows that EP has tremendous potential to target metastatic PCa cells and provides new avenues for therapeutic approaches for advanced PCa.

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Data availability

The data represented here are available upon request from the corresponding author.

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Acknowledgements

This study is partly supported by the Master in Medical Biotechnology Program, Department of Biomedical Science, UICOM, Rockford, IL.

Funding

This study is partly supported by the Master’s in Medical Biotechnology Program, Department of Biomedical Science, UICOM, Rockford, IL.

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Author notes

  1. Angela Samy and Mohamed Ali Hussein have contributed equally to the study.

Authors and Affiliations

  1. Department of Biomedical Sciences, University of Illinois College of Medicine, 1601 Parkview Avenue, Rockford, IL, 61107, USA

    Angela Samy, Mohamed Ali Hussein & Gnanasekar Munirathinam

  2. Department of Pharmaceutical Services, Children’s Cancer Hospital Egypt 57357, Cairo, Egypt

    Mohamed Ali Hussein

Authors
  1. Angela Samy
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Contributions

Conceptualization, A.S., M.H., and G.M.; methodology, A.S., M.H., and G.M.; writing original draft, A.S., M.H., writing, review, and editing A.S., M.H., and G.M.; supervision, G.M. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Gnanasekar Munirathinam.

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Samy, A., Hussein, M.A. & Munirathinam, G. Eprinomectin: a derivative of ivermectin suppresses growth and metastatic phenotypes of prostate cancer cells by targeting the β-catenin signaling pathway. J Cancer Res Clin Oncol 149, 9085–9104 (2023). https://doi.org/10.1007/s00432-023-04829-5

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