Health & Environmental Research Online (HERO)


Print Feedback Export to File
975868 
Journal Article 
Abstract 
Signaling events in apoptotic photokilling of 5-aminolevulinic acid-treated tumor cells: Inhibitory effects of nitric oxide 
Bhowmick, R; Girotti, AW 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S28-S28 
English 
WOS:000260867900068 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
Photodynamic therapy (PDT) employs a photosensitizing agent, molecular oxygen, and visible light to produce reactive oxygen species that kill tumor and tumor vasculature cells in a sitespecific manner. Nitric oxide (NO) produced by these cells could be pro-carcinogenic by inhibiting apoptosis and promoting angiogenesis and tumor growth. We recently showed that NO from spermine NONOate (SPNO) or activated macrophages make COH-BR1 breast tumor cells hyperresistant to photokilling sensitized by 5-aminolevulinic acid (ALA)-generated protoporphyrin IX (PpIX). Signaling events associated with this hyperresistance are examined here. ALA-treated COH-BR1 cells containing mitochondria-localized PpIX were irradiated with broad-band visible light in the absence and presence of SPNO. Apoptotic vs. necrotic cell death was assessed by fluorescence microscopy. Redox signaling associated with MAP kinase (ERK1/2, p38, JNK) phosphorylation-activation and heme oxygenase-1 (HO-1) upregulation was studied using immunoprecipitation and Western blot methodology. Irradiation of sensitized cells resulted in activation of pro-apoptotic p38α and JNK with concomitant deactivation of pro-survival p38β and ERK1/2. NO delivered during irradiation had an anti-apoptotic effect accompanied by substantially greater HO-1 induction and reversal of the effects seen without NO. Downstream of MAPK activation, we observed induction of pro-apoptotic Bax and repression of anti-apoptotic Bcl-xL, both responses being reversed by NO. These findings provide new insights into signaling activity associated with the intrinsic apoptotic pathway in ALA-PDT and how this activity can be modulated by NO. (Supported by NIH: CA70823) 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008