Inactivation of metabolic enzymes by photo-treatment with zinc meta N-methylpyridylporphyrin.
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 cross-linking 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.
Al-Mutairi
Dalal A
DA
Department of Biochemistry, Faculty of Medicine, Kuwait University, PO Box 24923 Safat, 13110, Kuwait.
Craik
James D
JD
Batinic-Haberle
Ines
I
Benov
Ludmil T
LT
D001711:Biotransformation / Q000187:drug effects; D045744:Cell Line, Tumor; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000493:pharmacokinetics*; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010789:Phototherapy; D015032:Zinc / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D008665:Metalloporphyrins; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D003577:Cytochrome P-450 Enzyme System; D017323:Dihematoporphyrin Ether; D015032:Zinc