Targeting autophagy by antipsychotic phenothiazines: potential drug repurposing for cancer therapy
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Le résumé fourni par la source
Cancer is recognized as the major cause of death worldwide and the most challenging public health issues. Tumor cells exhibit molecular adaptations and metabolic reprograming to sustain their high proliferative rate and autophagy plays a pivotal role to supply the high demand for metabolic substrates and for recycling cellular components, which has attracted the attention of the researchers. The modulation of the autophagic process sensitizes tumor cells to chemotherapy-induced cell death and reverts drug resistance. In this regard, many in vitro and in vivo studies having shown the anticancer activity of phenothiazine (PTZ) derivatives due to their potent cytotoxicity in tumor cells. Interestingly, PTZ have been used as antiemetics in antitumor chemotherapy-induced vomiting, maybe exerting a combined antitumor effect. Among the mechanisms of cytotoxicity, the modulation of autophagy by these drugs has been highlighted. Therefore, the use of PTZ derivatives can be considered as a repurposing strategy in antitumor chemotherapy. Here, we provided an overview of the effects of antipsychotic PTZ on autophagy in tumor cells, evidencing the molecular targets and discussing the underlying mechanisms. The modulation of autophagy by PTZ in tumor cells have been consistently related to their cytotoxic action. These effects depend on the derivative, their concentration, and also the type of cancer. Most data have shown the impairment of autophagic flux by PTZ, probably due to the blockade of lysosome-autophagosome fusion, but some studies have also suggested the induction of autophagy. These data highlight the therapeutic potential of targeting autophagy by PTZ in cancer chemotherapy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Targeting autophagy by antipsychotic phenothiazines: potential drug repurposing for cancer therapy
- Date Crossref
- 01/04/2024
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Universidade Federal do ABC pays non établi dans la noticeUniversité ou école supérieure
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Medical University of Silesia pays non établi dans la noticeUniversité ou école supérieure
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University of Silesia in Katowice pays non établi dans la noticeUniversité ou école supérieure
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Universidade Federal de São Paulo pays non établi dans la noticeUniversité ou école supérieure
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Federal University of ABC (UFABC) Center for Natural and Human Sciences (CCNH) pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Pharmaceutical Sciences in Sosnowiec Department of Drug and Cosmetics Technology pays non établi dans la noticeUniversité ou école supérieure
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Federal University of São Paulo (UNIFESP) Departament of Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
Universidade Federal do ABC, Medical University of Silesia et University of Silesia in Katowice, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.