Autor: |
Pagano E; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy., Venneri T; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy., Lucariello G; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy., Cicia D; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy., Brancaleone V; Department of Science, University of Basilicata, 85100 Potenza, Italy., Nanì MF; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy., Cacciola NA; Research Institute on Terrestrial Ecosystems, National Research Council of Italy (CNR), 80131 Naples, Italy., Capasso R; Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy., Izzo AA; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy., Borrelli F; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy., Romano B; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy. |
Abstrakt: |
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. |