Eprinomectin: a derivative of ivermectin suppresses growth ...

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. 

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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.

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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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