Cold-pressed extraction of perilla seed oil enriched with alpha-linolenic acid mitigates tumour progression and restores gut microbial homeostasis in the AOM/DSS mice model of colitis-associated colorectal cancer

by Chawin Korsirikoon, Peerapa Techaniyom, Aikkarach Kettawan, Thanaporn Rungruang, Chanatip Metheetrairut, Pinidphon Prombutara, Aurawan Kringkasemsee Kettawan

The present investigation explores into the influence of dietary nutrients, particularly alpha-linolenic acid (ALA), a plant-derived omega-3 fatty acid abundant in perilla seed oil (PSO), on the development of colitis-associated colorectal cancer (CRC). The study employs a mouse model to scrutinize the effects of ALA-rich PSO in the context of inflammation-driven CRC. Perilla seeds were subjected to oil extraction, and the nutritional composition of the obtained oil was analysed. Male ICR mice, initiated at four weeks of age, were subjected to diets comprising 5%, 10%, or 20% PSO, 10% fish oil, or 5% soybean oil. All groups, with the exception of the control group (5% soybean oil), underwent induction with azoxymethane (AOM) and dextran sulphate sodium (DSS) to instigate CRC. Disease development, colon samples, preneoplastic lesions, dysplasia, and biomarkers were meticulously evaluated. Furthermore, gut microbiota composition was elucidated through 16S rRNA sequencing. The analysis revealed that PSO contained 61.32% ALA and 783.90 mg/kg tocopherols. Mice subjected to diets comprising 5% soybean or 10% fish oil exhibited higher tumour incidence, burden, multiplicity, and aberrant crypt counts. Remarkably, these parameters were significantly reduced in mice fed a 5% PSO diet. Additionally, 5% PSO-fed mice displayed reduced proliferative and pro-inflammatory markers in colon tissues, coupled with an alleviation of AOM/DSS-induced gut dysbiosis. Notably, PSO demonstrated inhibitory effects on colitis-associated CRC in the AOM/DSS mice model, achieved through the suppression of proliferative and pro-inflammatory protein levels, and mitigation of gut dysbiosis, with discernible efficacy observed at a 5% dietary concentration.