Inactivation of metabolic enzymes by photo-treatment with zinc meta N-methylpyridylporphyrin.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Al-Mutairi, DA; Craik, JD; Batinic-Haberle, I; Benov, LT

Published Date

  • November 2007

Published In

Volume / Issue

  • 1770 / 11

Start / End Page

  • 1520 - 1527

PubMed ID

  • 17884296

Pubmed Central ID

  • 17884296

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/j.bbagen.2007.06.006

Language

  • eng

Conference Location

  • Netherlands