Phenothiazines and selenocompounds: A potential novel combination therapy of multidrug resistant cancer
Background/Aim: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. Materials and Methods: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination w...
| Autores: | , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/223468 |
| Acesso em linha: | http://hdl.handle.net/10261/223468 |
| Access Level: | acceso abierto |
| Palavra-chave: | Cancer Multidrug resistance T-lymphoma Phenothiazines Selenoesters Selenoanhydride Combination chemotherapy |
| Resumo: | Background/Aim: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. Materials and Methods: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. Results: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines. Conclusion: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, |
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