Mechanisms of antitumor action of methyl-3,5-diiodo-4-(4′- methoxyphenoxy)benzoate: Drug-induced protein dephosphorylations and inhibition of the permissive action of ceramide on growth factor induced cell proliferation

Pal I. Bauer, Eva Kirsten, Ernest Kun

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Abstract

The tumoricidal mechanism of methyl-3,5-diiodo- 4-(4′-methoxypropoxy) benzoate (DIME), or DIPE, has been analyzed beyond its first recognized cellular site, which is the inhibition of tubulin polymerization. DIME (or DIPE) pretreatment of Eras cells for 3 days abolished ceramide basic fibroblast growth factor (bFGF)-induced glycolysis, coinciding with a block produced by the phosphoprotein dephosphorylation of cdc 25 by protein phosphatase 2A (PP2A). Protein dephosphorylation is directly activated by DIME (or DIPE), and enzyme activities that are dependent on P-proteins are significantly down-regulated (e.g. Topo I and II, MAP-kinase, and cdc-cyclin kinase). Purified PP2A is one target of activation by DIME (or DIPE), and an alkaline phosphatase isoenzyme is also induced by the drug. It is proposed that the pleiotropic effects of DIME (or DIPE) on cancer cells involve the activation of protein dephosphorylations, as well as inhibition of tubulin polymerization.

Original languageEnglish
Pages (from-to)465-468
Number of pages4
JournalOncology Reports
Volume13
Issue number3
Publication statusPublished - Mar 1 2005

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Keywords

  • Basic fibroblast growth factor
  • Methyl-3,5-diiodo-4-(4′-methoxypropoxy)benzoate
  • Platelet-derived growth factor
  • Protein phosphatase 2A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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