Amino Acids

, Volume 39, Issue 3, pp 661–670

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
Original Article

DOI: 10.1007/s00726-010-0487-5

Cite this article as:
Stiuso, P., Giuberti, G., Lombardi, A. et al. Amino Acids (2010) 39: 661. doi:10.1007/s00726-010-0487-5

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 H2O2 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.

Keywords

AktExtracellular signal-regulated kinases Erk-1/2p38 kinaseOxidative stressProliferationVasoactive intestinal peptide (VIP)γ-Glutamyl 16 amine vasoactive intestinal peptide (VIP-DAP3)

Abbreviations

DMEM

Dulbecco’s modified Eagle medium

RPMI

Roswell Park Memorial Institute medium

KB

Human oropharyngeal epidermoid carcinoma

H1355

Lung epidermoid NSCLC

Dap

1,3-Diaminopropane

NO

Nitric oxide

PACAP

Pituitary adenylate cyclase-activating peptide

Pt

Put rescine

Spd

Spermidine

Spm

Spermine

TGase

Transglutaminase

VIP

Vasoactive intestinal peptide

VPAC1

V IP/PACAP1 receptor

VPAC2

V IP/PACAP2 receptor

VIP-DAP

γ-Glutamyl l6-diaminopropane derivative of vasoactive intestinal peptide

RP-HPLC

Reverse-phase HPLC

SOD

Superoxide dismutase

GPX

Glutathione peroxidase

p38 MAPK

p38 mitogen-activated protein kinases

SAPK/JNK

Stress-activated protein kinase/c-Jun NH2-terminal kinase

AKT

Serine/threonine kinase

GSK-3

Glycogen synthase kinase

HE

Hydroethidine

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Paola Stiuso
    • 1
  • Gaia Giuberti
    • 1
  • Angela Lombardi
    • 1
  • Alessandra Dicitore
    • 1
  • Vittorio Limongelli
    • 2
  • Maria Cartenì
    • 3
  • Alberto Abbruzzese
    • 1
  • Michele Caraglia
    • 1
  1. 1.Department of Biochemistry and BiophysicsSecond University of NaplesNaplesItaly
  2. 2.Department of Pharmaceutical and Toxicological ChemistryUniversity of Naples Federico IINaplesItaly
  3. 3.Department of Experimental MedicineSecond University of NaplesNaplesItaly