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Inhibition of pkc and pka by chemopreventive organoselenium compounds

P Foiles1, H Fujiki, M Suganuma

  • 1AMER HLTH FDN,NEW YORK,NY 10595. SAITAMA CANC CTR,RES INST,INA,SAITAMA 362,JAPAN.

International Journal of Oncology
|May 10, 2011
PubMed

Insights

1,4-phenylenebis(methylene)-selenocyanate (p-XSC) effectively inhibits protein kinases A and C, suggesting a mechanism for its chemopreventive properties. This organoselenium compound shows greater efficacy and lower toxicity than benzyl selenocyanate (BSC) or sodium selenite.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Organoselenium compounds are investigated for chemopreventive potential.
  • 1,4-phenylenebis(methylene)-selenocyanate (p-XSC) demonstrates superior efficacy and reduced toxicity compared to benzyl selenocyanate (BSC) and Na2SeO3 in rodent models.
  • The precise mechanisms underlying the chemopreventive effects of p-XSC require elucidation.

Purpose of the Study:

  • To investigate the effects of p-XSC on protein kinase A (PKA) and protein kinase C (PKC) activity.
  • To compare the inhibitory potential of p-XSC with BSC and Na2SeO3 on these kinases.
  • To explore the cellular effects of p-XSC, including protein phosphorylation and cell morphology changes.

Main Methods:

  • In vitro kinase assays to measure PKA and PKC inhibition.
  • Cell culture experiments using primary human fibroblasts and rat fibroblast (R6) cells.
  • Assessment of protein phosphorylation and morphological alterations in response to p-XSC treatment.

Main Results:

  • p-XSC completely inhibited both PKA and PKC activity with an EC50 of 0.1 μM.
  • BSC showed less potent inhibition, while Na2SeO3 had no significant effect on kinase activity.
  • p-XSC inhibited protein phosphorylation in human fibroblasts and altered rat fibroblast morphology, with additive effects when combined with staurosporine.

Conclusions:

  • The inhibition of PKA and PKC by p-XSC is a key mechanism contributing to its chemopreventive activity.
  • p-XSC represents a promising chemopreventive agent with a favorable efficacy and toxicity profile.
  • Further research into organoselenium compounds like p-XSC could lead to novel cancer prevention strategies.

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