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

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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.

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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

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy

    Paola Stiuso, Gaia Giuberti, Angela Lombardi, Alessandra Dicitore, Alberto Abbruzzese & Michele Caraglia

  2. Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Via D. Montesano 49, 80131, Naples, Italy

    Vittorio Limongelli

  3. Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy

    Maria Cartenì

Authors
  1. Paola Stiuso
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  2. Gaia Giuberti
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  3. Angela Lombardi
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  4. Alessandra Dicitore
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  5. Vittorio Limongelli
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  6. Maria Cartenì
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  7. Alberto Abbruzzese
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  8. Michele Caraglia
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Correspondence to Michele Caraglia.

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Stiuso, P., Giuberti, G., Lombardi, A. et al. γ-Glutamyl 16-diaminopropane derivative of vasoactive intestinal peptide: a potent anti-oxidative agent for human epidermoid cancer cells. Amino Acids 39, 661–670 (2010). https://doi.org/10.1007/s00726-010-0487-5

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  • DOI: https://doi.org/10.1007/s00726-010-0487-5

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