CO 009: A NOVEL PEPTIDE SELECTED FROM AN ALASCANNING REGULATES THE ONCOGENIC ACTIVITY OF NFKB IN CANCER CELLS

Excerpt:


J Pharm Pharmacogn Res 2(Suppl. 1): S5, 2014 Special supplement with the abstract book of LATINFARMA 2013 Oral Communication CO 009: A NOVEL PEPTIDE SELECTED FROM AN ALASCANNING REGULATES THE ONCOGENIC ACTIVITY OF NFKB IN CANCER CELLS Oliva B, Fernandez Jr, Gil J, Garay H, Reyes O, Guillen G, Vallespi GM. Center for Genetic Engineering … Continue reading CO 009: A NOVEL PEPTIDE SELECTED FROM AN ALASCANNING REGULATES THE ONCOGENIC ACTIVITY OF NFKB IN CANCER CELLS

J Pharm Pharmacogn Res 2(Suppl. 1): S5, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 009: A NOVEL PEPTIDE SELECTED FROM AN ALASCANNING REGULATES THE ONCOGENIC ACTIVITY OF NFKB IN CANCER CELLS

Oliva B, Fernandez Jr, Gil J, Garay H, Reyes O, Guillen G, Vallespi GM.

Center for Genetic Engineering and Biotechnology (CIGB), P.O.Box. 6162, Cubanacan, Playa, La Habana, Cuba.
Abstract

Introduction: The nuclear factor NFkB plays a critical role in diverse cellular processes associated with proliferation, cell death, as well as inflammation. Starting from a LPS-binding peptide from Limulus antiLPS factor, with powerful immunostimulatory activity, we have done alanine substitutions of particular residues and obtained a novel synthetic peptide (CIGB-552) that has lost its LPS binding capacity and is a powerful in vitro and in vivo cytotoxic agent. The potential mechanism responsible for the antitumor activity of CIGB-552 is based on a specific degradation of RelA (p65) and inhibition of NFkB regulated genes.

Material and methods: Cell lines: HT-29 (human colon cancer) and D122 (Lewis lung carcinoma). Female Balb/c mice were purchased from CENPALAB, Cuba. The peptide was synthesized manually using Fmoc/tBu solid phase.

Results: Here we demonstrate that treatment of tumor cells with the peptide CIGB-552 promotes the degradation of RelA (p65) and induces cell cycle arrest and apoptosis. In addition, the peptide inhibits gene products activated by NFkB, such as the anti-apoptotic protein Bcl-2. Here, we demonstrate that the CIGB-552 stabilizes a key protein in tumor cells, it which inhibits the transcription activity of NFkB. These findings provide evidence to support the regulation of transcription factor NFkB by the peptide CIGB- 552 in cancer cells. Furthermore, we demonstrate that CIGB-552 decrease tumor growth and increase survival in the human colon cancer xenograft HT-29 and shows anti-metastatic activity in a spontaneous metastatic model of the Lewis lung carcinoma.

Conclusion: Our finding points out to a novel mechanism by which the anti-apoptotic activity of NFkB can be regulated in cancer cells. Better understanding of the regulation of NFkB will provide a platform for development of specific therapeutic agents targeted towards the cancer-associated inflammation.

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