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Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects

SIMPLE SUMMARY: Treatment of colon cancer remains a significant unmet need. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide also present in food sources. PEA exerts intestinal anti-inflammatory effects, but knowledge of its role in colon carcinogenesis is still largely fragmentary. Her...

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Autores principales: Pagano, Ester, Venneri, Tommaso, Lucariello, Giuseppe, Cicia, Donatella, Brancaleone, Vincenzo, Nanì, M. Francesca, Cacciola, Nunzio A., Capasso, Raffaele, Izzo, Angelo A., Borrelli, Francesca, Romano, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073478/
https://www.ncbi.nlm.nih.gov/pubmed/33923494
http://dx.doi.org/10.3390/cancers13081923
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author Pagano, Ester
Venneri, Tommaso
Lucariello, Giuseppe
Cicia, Donatella
Brancaleone, Vincenzo
Nanì, M. Francesca
Cacciola, Nunzio A.
Capasso, Raffaele
Izzo, Angelo A.
Borrelli, Francesca
Romano, Barbara
author_facet Pagano, Ester
Venneri, Tommaso
Lucariello, Giuseppe
Cicia, Donatella
Brancaleone, Vincenzo
Nanì, M. Francesca
Cacciola, Nunzio A.
Capasso, Raffaele
Izzo, Angelo A.
Borrelli, Francesca
Romano, Barbara
author_sort Pagano, Ester
collection PubMed
description SIMPLE SUMMARY: Treatment of colon cancer remains a significant unmet need. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide also present in food sources. PEA exerts intestinal anti-inflammatory effects, but knowledge of its role in colon carcinogenesis is still largely fragmentary. Here, we found that ultramicronized PEA inhibited tumor cell proliferation mediated by PPAR-α and GPR55, induced cell cycle arrest in the G2/M phase and DNA fragmentation, reduced cell migration and exerted beneficial effects in the azoxymethane model of colonic tumors. Collectively, these data provide evidence on the beneficial effects of PEA in colon carcinogenesis. ABSTRACT: Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the endocannabinoid anandamide. PEA exerts intestinal anti-inflammatory effects, but knowledge of its role in colon carcinogenesis is still largely fragmentary. We deepened this aspect by studying the effects of PEA (ultramicronized PEA, um-PEA) on colon cancer cell proliferation, migration and cell cycle as well as its effects in a murine model of colon cancer. Results showed that um-PEA inhibited tumor cell proliferation via peroxisome proliferator-activated receptor α and G protein-coupled receptor 55, induced cell cycle arrest in the G2/M phase, possibly through cyclin B1/CDK1 upregulation, and induced DNA fragmentation. Furthermore, um-PEA reduced tumor cell migration by reducing MMP2 and TIMP1 expression. In vivo administration of um-PEA exerted beneficial effects in the azoxymethane model of colonic tumors, by reducing the number of preneoplastic lesions and tumors. Collectively, our findings provide novel proofs on the effects of um-PEA in colon carcinogenesis.
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spelling pubmed-80734782021-04-27 Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects Pagano, Ester Venneri, Tommaso Lucariello, Giuseppe Cicia, Donatella Brancaleone, Vincenzo Nanì, M. Francesca Cacciola, Nunzio A. Capasso, Raffaele Izzo, Angelo A. Borrelli, Francesca Romano, Barbara Cancers (Basel) Article SIMPLE SUMMARY: Treatment of colon cancer remains a significant unmet need. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide also present in food sources. PEA exerts intestinal anti-inflammatory effects, but knowledge of its role in colon carcinogenesis is still largely fragmentary. Here, we found that ultramicronized PEA inhibited tumor cell proliferation mediated by PPAR-α and GPR55, induced cell cycle arrest in the G2/M phase and DNA fragmentation, reduced cell migration and exerted beneficial effects in the azoxymethane model of colonic tumors. Collectively, these data provide evidence on the beneficial effects of PEA in colon carcinogenesis. ABSTRACT: Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the endocannabinoid anandamide. PEA exerts intestinal anti-inflammatory effects, but knowledge of its role in colon carcinogenesis is still largely fragmentary. We deepened this aspect by studying the effects of PEA (ultramicronized PEA, um-PEA) on colon cancer cell proliferation, migration and cell cycle as well as its effects in a murine model of colon cancer. Results showed that um-PEA inhibited tumor cell proliferation via peroxisome proliferator-activated receptor α and G protein-coupled receptor 55, induced cell cycle arrest in the G2/M phase, possibly through cyclin B1/CDK1 upregulation, and induced DNA fragmentation. Furthermore, um-PEA reduced tumor cell migration by reducing MMP2 and TIMP1 expression. In vivo administration of um-PEA exerted beneficial effects in the azoxymethane model of colonic tumors, by reducing the number of preneoplastic lesions and tumors. Collectively, our findings provide novel proofs on the effects of um-PEA in colon carcinogenesis. MDPI 2021-04-16 /pmc/articles/PMC8073478/ /pubmed/33923494 http://dx.doi.org/10.3390/cancers13081923 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pagano, Ester
Venneri, Tommaso
Lucariello, Giuseppe
Cicia, Donatella
Brancaleone, Vincenzo
Nanì, M. Francesca
Cacciola, Nunzio A.
Capasso, Raffaele
Izzo, Angelo A.
Borrelli, Francesca
Romano, Barbara
Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
title Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
title_full Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
title_fullStr Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
title_full_unstemmed Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
title_short Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
title_sort palmitoylethanolamide reduces colon cancer cell proliferation and migration, influences tumor cell cycle and exerts in vivo chemopreventive effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073478/
https://www.ncbi.nlm.nih.gov/pubmed/33923494
http://dx.doi.org/10.3390/cancers13081923
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