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

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

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Photochemical & Photobiological Sciences Vol - 8 Issue - 9

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

Content Provider	Royal Society of Chemistry (RSC)
Author	Sačková, Veronika Mikeš, Jaromír Koval', Ján Fedoročko, Peter Jendželovský, Rastislav Procházková, Jiřina Souček, Karel Hofmanová, Jiřina Kozubík, Alois Kello, Martin
Copyright Year	2009
Abstract	Photodynamic therapy (PDT) is a flexible multi-target therapeutic approach. One of the main requirements of successful PDT is sufficient intracellular concentration of an applicable photosensitizer. 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. The interaction of hypericin with this cell drug-defence system is still unclear. 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. In conclusion, our study suggests that drug efflux transporters MRP1 and BCRP affect the pharmacokinetics of hypericin in HT-29 colon adenocarcinoma cells, and the action of hypericin-mediated PDT (HY-PDT) should be modulated by pre-treatment with their specific inhibitors.
Starting Page	1716
Ending Page	1723
Page Count	8
File Format	HTM / HTML PDF
ISSN	1474905X
Volume Number	8
Issue Number	12
Journal	Photochemical & Photobiological Sciences
DOI	10.1039/b9pp00086k
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Adenocarcinoma Oxidative stress ABC Proadifen Photodynamic therapy Cytochrome P450 Breast cancer Protein P-glycoprotein Hypericin Caspase 3 Membrane potential ATP-binding cassette transporter Pharmacokinetics Photosensitizer Cancer Apoptosis
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry

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