Open AccessHeme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity
Author(s) -
Dominika Nowis,
Magdalena Legat,
Tomasz Grzela,
Justyiderla,
Ewa Wilczek,
Grzegorz M. Wilczyński,
Eliza Głodkowska,
Piotr Mrówka,
Tadeusz Issat,
Józef Dulak,
Alicja Józkowicz,
Halina Waś,
Mariusz Adamek,
Antoni Wrzosek,
Sławomir Nazarewski,
Marcin Makowski,
Tomasz Stokłosa,
Marek Jakóbisiak,
Jakub Gołąb
Publication year - 2006
Publication title -
oncogene
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/sj.onc.1209378
Subject(s) - heme oxygenase , biliverdin , photodynamic therapy , cytotoxicity , cytoprotection , cancer research , heme , biology , phototoxicity , hemin , dna damage , transfection , reactive oxygen species , protoporphyrin ix , pharmacology , biochemistry , apoptosis , chemistry , in vitro , enzyme , dna , organic chemistry , gene
Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.