Publication details

Drug efflux transporters, MRP1 and BCRP, affect the outcome of hypericin-mediated photodynamic therapy in HT-29 adenocarcinoma cells

Authors

JENDZELOVSKY Rastislav MIKES Jaromir KOVAL Jan SOUČEK Karel PROCHÁZKOVÁ Jiřina KELLO Martin SACKOVA Veronika HOFMANOVÁ Jiřina KOZUBÍK Alois FEDOROČKO Peter

Year of publication 2009
Type Article in Periodical
Magazine / Source PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
MU Faculty or unit

Faculty of Science

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.

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