Enzymatic mechanism of the tumoricidal action of 4-iodo-3-nitrobenzamide

  • Authors:
    • Ernest Kun
    • Jerome Mendeleyev
    • Alaeddin Hakam
    • Eva Kirsten
  • View Affiliations

  • Published online on: September 1, 2009     https://doi.org/10.3892/mmr_00000165
  • Pages: 739-742
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Abstract

Activation of the prodrug 4-iodo-3-nitrobenzamide critically depends on the cellular reducing system specific to cancer cells. In non-malignant cells, reduction of this prodrug to the non-toxic amine occurs by the flavoprotein of complex?I of mitochondria receiving Mg2+-ATP-dependent reducing equivalents from NADH to NADPH via pyridine nucleotide transhydrogenation. This hydride transfer is deficient in malignant cells; therefore, the lethal synthesis of 4-iodo-3-nitrosobenzamide takes place selectively. Enzymatic evidence for this mechanism has been provided by cellular studies with lysolecithin-permeabilized cells and cell fractions, which have identified the defect in transhydrogenation in neoplastic cells to be located at the energy transfer site. Confirming previous results, the present study demonstrates the validity of the selective tumoricidal action of the prodrug in cell cultures.

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September-October 2009
Volume 2 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Kun E, Mendeleyev J, Hakam A and Kirsten E: Enzymatic mechanism of the tumoricidal action of 4-iodo-3-nitrobenzamide. Mol Med Rep 2: 739-742, 2009.
APA
Kun, E., Mendeleyev, J., Hakam, A., & Kirsten, E. (2009). Enzymatic mechanism of the tumoricidal action of 4-iodo-3-nitrobenzamide. Molecular Medicine Reports, 2, 739-742. https://doi.org/10.3892/mmr_00000165
MLA
Kun, E., Mendeleyev, J., Hakam, A., Kirsten, E."Enzymatic mechanism of the tumoricidal action of 4-iodo-3-nitrobenzamide". Molecular Medicine Reports 2.5 (2009): 739-742.
Chicago
Kun, E., Mendeleyev, J., Hakam, A., Kirsten, E."Enzymatic mechanism of the tumoricidal action of 4-iodo-3-nitrobenzamide". Molecular Medicine Reports 2, no. 5 (2009): 739-742. https://doi.org/10.3892/mmr_00000165