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01-06-2020 | Ivermectin | Original Article

Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug

Authors: Mandy Juarez, Alejandro Schcolnik-Cabrera, Guadalupe Dominguez-Gomez, Alma Chavez-Blanco, Jose Diaz-Chavez, Alfonso Duenas-Gonzalez

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2020

Abstract

Purpose

Ivermectin is an antiparasitic drug that exhibits antitumor effects in preclinical studies, and as such is currently being repositioned for cancer treatment. However, divergences exist regarding its employed doses in preclinical works. Therefore, the aim of this study was to determine whether the antitumor effects of ivermectin are observable at clinically feasible drug concentrations.

Methods

Twenty-eight malignant cell lines were treated with 5 μM ivermectin. Cell viability, clonogenicity, cell cycle, cell death and pharmacological interaction with common cytotoxic drugs were assessed, as well as the consequences of its use on stem cell-enriched populations. The antitumor in vivo effects of ivermectin were also evaluated.

Results

The breast MDA-MB-231, MDA-MB-468, and MCF-7, and the ovarian SKOV-3, were the most sensitive cancer cell lines to ivermectin. Conversely, the prostate cancer cell line DU145 was the most resistant to its use. In the most sensitive cells, ivermectin induced cell cycle arrest at G₀–G₁ phase, with modulation of proteins associated with cell cycle control. Furthermore, ivermectin was synergistic with docetaxel, cyclophosphamide and tamoxifen. Ivermectin reduced both cell viability and colony formation capacity in the stem cell-enriched population as compared with the parental one. Finally, in tumor-bearing mice ivermectin successfully reduced both tumor size and weight.

Conclusion

Our results on the antitumor effects of ivermectin support its clinical testing.

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Title: Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug
Authors: Mandy Juarez
Alejandro Schcolnik-Cabrera
Guadalupe Dominguez-Gomez
Alma Chavez-Blanco
Jose Diaz-Chavez
Alfonso Duenas-Gonzalez
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keywords: Ivermectin
Tamoxifen
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04041-z

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