title: Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells.
abstract: One proposal to increase the efficiency of photodynamic therapy (PDT) is to accompany photosensitization with other treatment modalities, including modulation of arachidonic acid (AA) metabolism. The aim of this study was to evaluate the effectiveness of a combined modality approach employing 48 and 24 h pretreatment with various inhibitors of lipoxygenase (LOX; nordihydroguaiaretic acid, esculetin, AA-861, MK-886 and baicalein), cyclooxygenase (COX; diclofenac, flurbiprofen, ibuprofen, indomethacin, SC-560 and rofecoxib) and cytochrome P450-monooxygenase (proadifen) pathways, followed by hypericin-mediated PDT. Cytokinetic parameters like MTT assay, adherent and floating cell numbers, viability and cell cycle distribution analysis were examined 24 h after hypericin activation. Pretreatment of human colon cancer cells HT-29 prior to PDT with 5-LOX inhibitor MK-886 as well as 5, 12-LOX and 12-LOX inhibitors (esculetin and baicalein, respectively) resulted in significant and dose-dependent effects on all parameters tested. Pretreatment with diclofenac, flurbiprofen, ibuprofen and indomethacin, the nonspecific COX inhibitors, promoted hypericin-mediated PDT, but these effects were probably COX-independent. In contrast, application of SC-560 and rofecoxib, specific inhibitors of COX-1 and COX-2, respectively, attenuated PDT. Inhibition of P450 monooxygenase with proadifen implied also the significance of this metabolic pathway in cell survival and cell resistance to hypericin photocytotoxicity. In conclusion, our results testify that application of diverse inhibitors of AA metabolism may have different consequences on cellular response to hypericin-mediated PDT and that some of them could be considered for potentiation of PDT.
authors: Institute of Biology and Ecology, Faculty of Sciences, P. J. Safárik University, Kosice, Slovakia.
authors: Ján
authors: J
authors: Kleban
authors: Jaromír
authors: J
authors: Mikes
authors: Beáta
authors: B
authors: Szilárdiová
authors: Ján
authors: J
authors: Koval
authors: Veronika
authors: V
authors: Sacková
authors: Peter
authors: P
authors: Solár
authors: Viktor
authors: V
authors: Horváth
authors: Jirina
authors: J
authors: Hofmanová
authors: Alois
authors: A
authors: Kozubík
authors: Peter
authors: P
authors: Fedorocko
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000873:Anthracenes; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy
chemical_list: D000873:Anthracenes; D016718:Arachidonic Acid; D010569:Perylene; C004965:hypericin