Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug
- PMID: 32474842
- DOI: 10.1007/s00280-020-04041-z
Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug
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.
Keywords: Cancer; Cancer stem cells; Drug repurposing; Ivermectin.
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References
-
- Omura S, Crump A (2004) The life and times of ivermectin—a success story. Nat Rev Microbiol 2(12):984–989. https://doi.org/10.1038/nrmicro1048 - DOI - PubMed
-
- Omura S (2008) Ivermectin: 25 years and still going strong. Int J Antimicrob Agents 31(2):91–98. https://doi.org/10.1016/j.ijantimicag.2007.08.023 - DOI - PubMed
-
- Chabala JC, Mrozik H, Tolman RL, Eskola P, Lusi A, Peterson LH, Woods MF, Fisher MH, Campbell WC, Egerton JR, Ostlind DA (1980) Ivermectin, a new broad-spectrum antiparasitic agent. J Med Chem 23(10):1134–1136. https://doi.org/10.1021/jm00184a014 - DOI - PubMed
-
- Goa KL, McTavish D, Clissold SP (1991) Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs 42(4):640–658. https://doi.org/10.2165/00003495-199142040-00007 - DOI - PubMed
-
- Kumaraswami V, Ottesen EA, Vijayasekaran V, Devi U, Swaminathan M, Aziz MA, Sarma GR, Prabhakar R, Tripathy SP (1988) Ivermectin for the treatment of Wuchereria bancrofti filariasis. Efficacy and adverse reactions. JAMA 259(21):3150–3153 - DOI
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