Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1770, Issue 11, Pages 1520-1527Publisher
ELSEVIER
DOI: 10.1016/j.bbagen.2007.06.006
Keywords
photodynamic therapy; Zn meta N-methylpyridylporphyrin; enzyme inactivation; NADPH production; cancer cell glycolysis; MTT reduction; inhibition of metabolism
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Funding
- NIAID NIH HHS [WU19 AI67798-01, U19 AI067798] Funding Source: Medline
- NIEHS NIH HHS [IR21-ES0/3682] Funding Source: Medline
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Cell proliferation is notably dependent on energy supply and generation of reducing equivalents in the form of NADPH for reductive biosynthesis. Blockage of pathways generating energy and reducing equivalents has proved successful for cancer treatment. We have previously reported that isomeric Zn(II) N-methylpyridylporphyrins (ZnTM-2(3,4)-PyP4+) can act as photosensitizers, preventing cell proliferation and causing cell death in vitro. The present study demonstrates that upon illumination, ZnTM-3-PyP inactivates glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, NADP(+) -linked isocitrate dehydrogenase, aconitase, and fumarase in adenocarcinoma LS174T cells. ZnTM-3-PyP4+ was significantly more effective than hematoporphyrin derivative (HpD) for inactivation of all enzymes, except aconitase and isocitrate dehydrogenase. Enzyme inactivation was accompanied by aggregation, presumably due to protein crosslinking of some of the enzymes tested. Inactivation of metabolic enzymes caused disruption of cancer cells' metabolism and is likely to be one of the major reasons for antiproliferative activity of ZnTM-3-PyP. (C) 2007 Elsevier B.V. All rights reserved.
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