γ-Glutamyl 16-diaminopropane derivative of vasoactive intestinal peptide: A potent anti-oxidative agent for human epidermoid cancer cells

Paola Stiuso, Gaia Giuberti, Angela Lombardi, Alessandra Dicitore, Vittorio Limongelli, Maria Cartenì, Alberto Abbruzzese, Michele Caraglia

Research output: Contribution to journalArticlepeer-review

Abstract

We previously demonstrated that the γ-glutamyl 16 amine derivative of vasoactive intestinal peptide (VIP) acts as structural VIP agonist with affinity and potency higher than VIP. Herein, we have evaluated the effects of VIP and γ-Gln16-diaminopropane derivative of VIP (VIP-DAP3) on the proliferation and protection from oxidative stress induced by hydrogen peroxide (H2O2) on epidermoid carcinoma cell lines. We have found that 10-11 M VIP-DAP3 completely antagonized the inhibition induced by H2O2 on both cell proliferation and S-phase distribution while these effects were only partially antagonized by equimolar concentrations of VIP. Moreover, both oxidative stress and intracellular lipid oxidation induced by H2O2 were reduced by VIP and completely antagonized by VIP-DAP3. Thereafter, we have found that H 2O2 increased p38 kinase activity and both HSP70 and HSP27 expression. VIP and VIP-DAP3 again antagonized these effects partially or totally, respectively. H2O2 reduced the activity of extracellular signal-regulated kinases Erk-1/2 and Akt, signalling proteins involved in proliferation/survival pathways. Again VIP restored the activity of both kinases while VIP-DAP3 caused indeed an increase of their activity as compared to untreated cells. These data suggest that VIP-DAP3 has a stronger anti-oxidative activity as compared to VIP likely based on its super-agonistic binding on the putative receptor.

Original languageEnglish
Pages (from-to)661-670
Number of pages10
JournalAmino Acids
Volume39
Issue number3
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Akt
  • Extracellular signal-regulated kinases Erk-1/2
  • Oxidative stress
  • P38 kinase
  • Proliferation
  • Vasoactive intestinal peptide (VIP) γ-Glutamyl 16 amine vasoactive intestinal peptide (VIP-DAP3

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry
  • Medicine(all)

Fingerprint

Dive into the research topics of 'γ-Glutamyl 16-diaminopropane derivative of vasoactive intestinal peptide: A potent anti-oxidative agent for human epidermoid cancer cells'. Together they form a unique fingerprint.

Cite this