NEMO-binding domain peptide inhibits proliferation of human melanoma cells.
Melanoma is the most aggressive form of skin cancer, it originates from melanocytes and its incidence has increased in the last decade. Recent advances in the understanding of the underlying biology of the progression of melanoma have identified key signalling pathways that are important in promoting melanoma tumourigenesis, thus providing dynamic targets for therapy. One such important target identified in melanoma tumour progression is the Nuclear Factor-kappaB (NF-kappaB) pathway. In vitro studies have shown that NF-kappaB binding is constitutively elevated in human melanoma cultures compared to normal melanocytes. It has been found that a short cell-permeable peptide spanning the IKK-beta NBD, named NBD peptide, disrupted the association of NEMO with IKKs in vitro and blocked TNFalpha-induced NF-kappaB activation in vivo. In the present study we investigated the effect of the NBD peptide on NF-kappaB activity and survival of A375 human melanoma cells. We found that NBD peptide is able to inhibit the proliferation of A375 cells, which present constitutively elevated NF-kappaB levels. Inhibition of cell proliferation by NBD peptide was associated with direct inhibition of constitutive NF-kappaB DNA-binding activity and induction of apoptosis by activation of caspase-3 as confirmed by the cleavage and consequently inactivation of poly (ADP ribose) polymerase (PARP-1) known as the best marker of this process.
Ianaro
Angela
A
Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy. ianaro@unina.it
Tersigni
Mariaroberta
M
Belardo
Giuseppe
G
Di Martino
Silvana
S
Napolitano
Maria
M
Palmieri
Giuseppe
G
Sini
MariaCristina
M
De Maio
Anna
A
Ombra
MariaNeve
M
Gentilcore
Giuseppina
G
Capone
Mariaelena
M
Ascierto
MariaLibera
M
Satriano
Rocco Alfredo
RA
Farina
Benedetta
B
Faraone-Mennella
MariaRosaria
M
Ascierto
Paolo Antonio
PA
Ialenti
Armando
A
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology*; D008545:Melanoma / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism
C491731:IKBKG protein, human; D016328:NF-kappa B; D051550:I-kappa B Kinase