title: Photoactivated hypericin increases the expression of SOD-2 and makes MCF-7 cells resistant to photodynamic therapy.
abstract: Photoactivated hypericin increased production of reactive oxygen species in human breast adenocarcinoma MCF-7 as well as in MDA-MB-231 cells 1h after photodynamic therapy. On the other hand, reactive oxygen species dropped 3h after photodynamic therapy with hypericin, but only in MCF-7 cells, whereas in MDA-MB-231 cells remained elevated. The difference in the dynamics of reactive oxygen species after hypericin activation was related to increased activity of SOD-2 in MCF-7 cells compared to MDA-MB-231 cells. Indeed, photodynamic therapy with hypericin significantly increased SOD-2 activity in MCF-7 cells, but only slightly in MDA-MB-231 cells. In this regard, SOD-2 activity correlated well with enhanced both mRNA expression as well as SOD-2 protein level in MCF-7 cells. The role of SOD-2 in the resistance of MCF-7 cells to photodynamic therapy with hypericin was monitored using SOD-2 inhibitor - 2-methoxyestradiol. Interestingly, the combination of photodynamic therapy with hypericin and methoxyestradiol sensitized MCF-7 cells to photodynamic therapy and significantly reduced its clonogenic ability. Furthermore, methoxyestradiol potentiated the activation of caspase 3/7 and apoptosis induced by photodynamic therapy with hypericin.
authors.affiliation: Laboratory of Cell Biology, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 04001 Košice, Slovak Republic.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Kimáková
authors.affiliation: Laboratory of Cell Biology, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 04001 Košice, Slovak Republic. Electronic address: peter.solar@upjs.sk.
authors.forename: Peter
authors.initials: P
authors.lastname: Solár
authors.affiliation: Laboratory of Cell Biology, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 04001 Košice, Slovak Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Fecková
authors.affiliation: Laboratory of Cell Biology, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 04001 Košice, Slovak Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sačková
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, P.J. Šafárik University in Košice, 04001 Košice, Slovak Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Solárová
authors.affiliation: Laboratory of Cell Biology, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 04001 Košice, Slovak Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Ilkovičová
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, P.J. Šafárik University in Košice, 04001 Košice, Slovak Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kello
mesh_terms: D000077584:2-Methoxyestradiol; D000230:Adenocarcinoma / Q000628:therapy*; D000873:Anthracenes; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008027:Light; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000099156:Superoxide Dismutase 2
chemical_list: D000077584:2-Methoxyestradiol; D000873:Anthracenes; D004958:Estradiol; D010569:Perylene; D017319:Photosensitizing Agents; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C004965:hypericin
keywords: Hypericin; MCF-7; Photodynamic therapy; Resistance; SOD-2