Emu oil and grape seed extract reduce tumour burden and disease parameters in murine colitis-associated colorectal cancer

Abstract

Ulcerative colitis (UC) is an incurable condition whereby patients are at an increased risk of developing colorectal cancer (CRC). We aimed to investigate the combination of Emu Oil and grape seed extract (GSE) in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of colitis-associated CRC (CA-CRC). C57BL/6 mice (n=10/group) were injected i.p. with saline or AOM (7.4mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80μL), EO (80μL), GSE (80μL; 400mg/kg) or combined EO/GSE (160μL). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max -21%) and increased DAI (max +83%) throughout the trial (p<0.05). EO (max -53%), GSE (max -51%) and EO/GSE (max -71%) reduced DAI scores in AOM/DSS mice in all DSS cycles (p<0.05). EO/GSE-treatment in AOM/DSS mice resulted in further DAI reduction compared to EO (max -62%) and GSE (max -71%) alone (p<0.05). AOM/DSS mice presented with severe colonoscopically-assessed colitis at all time-points, which was reduced by EO, GSE and EO/GSE (p<0.05). EO, GSE and EO/GSE reduced the number of colonic tumours compared to AOM/DSS controls (p<0.05). Myeloperoxidase (acute inflammation) and FITC-dextran levels (intestinal permeability) were increased in AOM/DSS controls (p<0.05). EO (-58%) and EO/GSE (-77%) reduced FITC-dextran compared to AOM/DSS controls (p<0.05), with no effect on MPO. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared to saline (p<0.05), with no effect observed following treatment. The combination of EO and GSE improved clinical indicators and reduced colonic tumours in AOM/DSS treated mice, suggesting potential in CA-CRC management.