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Apoptosis-accommodating Effect of Nitric Oxide in Photodynamically Stressed Tumor Cells

Authors

  • Magdalena Niziolek-Kierecka,

    1. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI
    2. Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Anna Pilat,

    1. Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Witold Korytowski,

    1. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI
    2. Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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  • Albert W. Girotti

    Corresponding author
    1. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI
      Corresponding author email: agirotti@mcw.edu (Albert W. Girotti)
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Corresponding author email: agirotti@mcw.edu (Albert W. Girotti)

Abstract

Using a 5-aminolevulinic acid (ALA)-photodynamic therapy model, we have discovered a new effect of nitric oxide (NO)—the ability to accommodate apoptosis. When sensitized by disseminated ALA-generated protoporphyrin IX, COH-BR1 tumor cells in glucose-containing medium died mainly by necrosis with a low level of apoptosis. Introduced before light at a nontoxic concentration, the NO donor SPNO inhibited necrosis, but supported apoptosis such that the latter became predominant in the remaining cell death. Accompanying this was a large increase in caspase-3/7 activation. SPNO-supported apoptosis was more pronounced when glucose-deprived cells were compared with glucose-replenished, SPNO-treated counterparts. SPNO plus glucose also suppressed plasma membrane-damaging lipid peroxidation and loss of cellular ATP under photostress. The NO effect is attributed to membrane protection with maintenance of sufficient glycolytic ATP to sustain apoptosis.

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