Breast cancer resistance protein is the enemy of hypericin accumulation and toxicity of hypericin-mediated photodynamic therapy - 09/12/18
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Graphical abstract |
Highlights |
• | Hypericin (HY) is a preferential substrate of ABC transporter BCRP. |
• | BCRP negatively affects the cytotoxic action of HY-mediated photodynamic therapy (HY-PDT). |
• | Inhibition of BCRP reverses the resistance to HY-PDT. |
• | Determination of BCRP expression may be crucial for therapy and diagnosis using HY. |
Abstract |
Breast cancer resistance protein (BCRP) belongs to the family of ATP-binding cassette (ABC) transporters, overexpression of which can confer a multidrug-resistant phenotype in cancer cells and tumors. BCRP mediates efflux of numerous xenobiotics, including various chemotherapeutic agents and photosensitizers. Hypericin (HY) is a naturally-occurring photosensitizer synthesized by plants of the genus Hypericum. Our recently published results indicate that accumulation of HY in cancer cells of different tissue origin can be affected mostly by BCRP. Considering all known facts, the main goal of this study was to verify whether not only HY accumulation but also toxicity of HY-mediated photodynamic therapy (PDT) can be affected by the presence of some ABC transporters. To specifically prove our hypothesis, we used an experimental model of human leukemia cell lines differing in the expression level of the main drug efflux transporters P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and BCRP. The lowest HY accumulation, and consequently the highest resistance to HY-PDT, was found in cells overexpressing BCRP. Moreover, pretreatment with BCRP inhibitor Ko143 significantly increased HY accumulation and sensitized cells to HY-PDT. Therefore, our findings represent direct evidence that BCRP is the nemesis of HY accumulation and toxicity of HY-PDT. Thus, we should emphasize that individualized screening for BCRP expression and activity may represent a useful tool for prediction of HY-mediated photodynamic diagnosis (PDD) or PDT effectiveness.
El texto completo de este artículo está disponible en PDF.Keywords : Hypericin, Photodynamic therapy, ABC transporters, Breast cancer resistance protein, Promyelocytic leukemia
Esquema
Vol 109
P. 2173-2181 - janvier 2019 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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