Tamoxifen Twists Again: On and Off-Targets in Macrophages and Infections.

Autor:	Sfogliarini C; Department of Pharmaceutical Sciences, University of Milan, Milan, Italy., Pepe G; Department of Pharmaceutical Sciences, University of Milan, Milan, Italy., Dolce A; Department of Pharmaceutical Sciences, University of Milan, Milan, Italy., Della Torre S; Department of Pharmaceutical Sciences, University of Milan, Milan, Italy., Cesta MC; Dompé Farmaceutici S.p.A., L'Aquila, Italy., Allegretti M; Dompé Farmaceutici S.p.A., L'Aquila, Italy., Locati M; IRCCS Humanitas Research Hospital, Rozzano, Italy.; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy., Vegeto E; Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2022 Mar 30; Vol. 13, pp. 879020. Date of Electronic Publication: 2022 Mar 30 (Print Publication: 2022).
DOI:	10.3389/fphar.2022.879020
Abstrakt:	Beyond the wide use of tamoxifen in breast cancer chemotherapy due to its estrogen receptor antagonist activity, this drug is being assayed in repurposing strategies against a number of microbial infections. We conducted a literature search on the evidence related with tamoxifen activity in macrophages, since these immune cells participate as a first line-defense against pathogen invasion. Consistent data indicate the existence of estrogen receptor-independent targets of tamoxifen in macrophages that include lipid mediators and signaling pathways, such as NRF2 and caspase-1, which allow these cells to undergo phenotypic adaptation and potentiate the inflammatory response, without the induction of cell death. Thus, these lines of evidence suggest that the widespread antimicrobial activity of this drug can be ascribed, at least in part, to the potentiation of the host innate immunity. This widens our understanding of the pharmacological activity of tamoxifen with relevant therapeutic implications for infections and other clinical indications that may benefit from the immunomodulatory effects of this drug. Competing Interests: MCC and MA were employed by Dompé Farmaceutici S.p.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Sfogliarini, Pepe, Dolce, Della Torre, Cesta, Allegretti, Locati and Vegeto.)
Databáze:	MEDLINE
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