Premium
Signaling Events in Nitric Oxide‐Induced Tumor Cell Resistance to Photodynamic Eradication
Author(s) -
Bhowmick Reshma,
Girotti Albert W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.646.2
Subject(s) - apoptosis , p38 mitogen activated protein kinases , reactive oxygen species , nitric oxide , photodynamic therapy , chemistry , heme , signal transduction , angiogenesis , heme oxygenase , downregulation and upregulation , kinase , protoporphyrin ix , nitric oxide synthase , microbiology and biotechnology , cancer research , oxidative stress , biology , biochemistry , mapk/erk pathway , enzyme , organic chemistry , gene
Purpose Photodynamic Therapy (PDT) is an antitumor modality that employs a photosensitizing agent, molecular oxygen, and visible light to produce reactive species that kill tumor/tumor vasculature cells in a site‐specific manner. Nitric oxide (NO) at low levels can inhibit apoptosis and promote angiogenesis and tumor growth. We showed recently that NO from a chemical donor/activated macrophages induced a resistance to photokilling in protoporphyrin IX (PpIX)‐sensitized COH‐BR1 breast tumor cells. Signaling events associated with this hyperresistance was examined in the present study. Methods COH‐BR1 cells were sensitized with PpIX in mitochondria via metabolism of ALA and irradiated in the presence/absence of SPNO‐derived NO. Apoptotic/necrotic photokillling was assessed by fluorescence microscopy using Hoechst/PI staining. Redox signaling associated with MAP kinase phosphorylation‐activation and heme oxygenase‐1 (HO‐1) upregulation was examined by immunoblotting. Results NO delivered during irradiation of ALA‐treated cells protected them against apoptotic death. This was accompanied by a large induction of HO‐1 and an increase in the activation of overall p38 and ERK1/2, but not JNK. Conclusions These findings suggest that antioxidant stress protein, HO‐1 plays a major role in NO's anti‐PDT effects and is associated with activation of the anti‐apoptotic p38 and ERK1/2 signaling pathways.