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Publication details
Drug efflux transporters, MRP1 and BCRP, affect the outcome of hypericin-mediated photodynamic therapy in HT-29 adenocarcinoma cells
Authors | |
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Year of publication | 2009 |
Type | Article in Periodical |
Magazine / Source | PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES |
MU Faculty or unit | |
Citation | |
Field | Oncology and hematology |
Keywords | MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; JOHNS-WORT; MXR ABCG2; METABOLISM; TOXICITY; INHIBITORS; INDUCTION; MODULATION; EXPRESSION |
Description | Photodynamic therapy (PDT) is a flexible multi-target therapeutic approach. Mechanisms of anticancer drug elimination by tumour cells are mostly linked to the elevated expression and activity of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein (BCRP) and P450 monooxygenases. We report here for the first time increased activity of MRP1 and BCRP in HT-29 colon cancer cells treated with hypericin per se. On the contrary, pre-treatment with proadifen (SKF525A) affected the function of MRP1 and BCRP leading to increased hypericin content, which might indicate a possible link between proadifen and these ABC transporter proteins. Subsequent enhanced intracellular oxidative stress was accompanied by loss of mitochondrial membrane potential, activation of caspase-9 and -3, PARP cleavage and onset of apoptosis. |