NEMO-binding domain peptide inhibits proliferation of human melanoma cells

Angela Ianaro, Mariaroberta Tersigni, Giuseppe Belardo, Silvana Di Martino, Maria Napolitano, Giuseppe Palmieri, MariaCristina Sini, Anna De Maio, MariaNeve Ombra, Giuseppina Gentilcore, Mariaelena Capone, MariaLibera Ascierto, Rocco Alfredo Satriano, Benedetta Farina, MariaRosaria Faraone-Mennella, Paolo Antonio Ascierto, Armando Ialenti

Research output: Contribution to journalArticle

Abstract

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-κB (NF-κB) pathway. In vitro studies have shown that NF-κB 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-β NBD, named NBD peptide, disrupted the association of NEMO with IKKs in vitro and blocked TNFα-induced NF-κB activation in vivo. In the present study we investigated the effect of the NBD peptide on NF-κB 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-κB levels. Inhibition of cell proliferation by NBD peptide was associated with direct inhibition of constitutive NF-κB 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.

Original languageEnglish
Pages (from-to)331-336
Number of pages6
JournalCancer Letters
Volume274
Issue number2
DOIs
Publication statusPublished - Feb 18 2009

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Keywords

  • Apoptosis
  • Melanoma
  • NBD peptide
  • NF-κB

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ianaro, A., Tersigni, M., Belardo, G., Martino, S. D., Napolitano, M., Palmieri, G., Sini, M., Maio, A. D., Ombra, M., Gentilcore, G., Capone, M., Ascierto, M., Satriano, R. A., Farina, B., Faraone-Mennella, M., Ascierto, P. A., & Ialenti, A. (2009). NEMO-binding domain peptide inhibits proliferation of human melanoma cells. Cancer Letters, 274(2), 331-336. https://doi.org/10.1016/j.canlet.2008.09.038