Anticancer activity of raw and digested Irish seaweed extracts on colorectal cancer models in vitro

Abstract

The aetiology of colorectal cancer, the third most prevalent cancer in the world, is linked to several risk factors, including age, genetic factors and diet. Seaweed consumption has been negatively correlated with colorectal cancer risk within Asian populations, and the anti-cancer properties of certain seaweed species have also been demonstrated within in vitro and animal models. The focus of this study was to examine the anti-cancer potential of selected Irish seaweed species, namely Ascophyllum nodosum, Laminaria digitata, Palmaria palmata and Ulva intestinalis using in vitro cell models of colon cancer. In order to account for the compositional changes occurring during gastrointestinal digestion, seaweed samples were subjected to in vitro simulation of gastric and pancreatic digestion. The chemopreventive properties of crude and digested seaweed treatments were tested using cell models, representing the key stages of colorectal cancer initiation, promotion and invasion.

Of the tested seaweed species A. nodosum had the highest polyphenol-content and antioxidant power, both reduced by > 60% after in vitro gastrointestinal digestion. Yet, digested A. nodosum extracts had a strong anti-genotoxic activity, connected to up-regulation of a detoxifying enzyme GSTκ-1. All crude and digested treatments had anti-proliferative effects in all cell types, inducing a necroptotic, mitochondrial cell death pathway with the up-regulation of AIF, JNK, Bax and PTEN. Digested extracts simultaneously induced the inflammatory or stress-related PI3K pathway, inhibiting the expression of Caspase-8 and p53. The invasion and migration of metastatic HT115 cells was inhibited by P. palmata treatments both pre- and post-digestion, the up-regulation of an anti-invasive tissue inhibitor of metalloproteinases TIMP-2 was observed.

Overall this work has demonstrated, for the first time, how a simulated gastrointestinal digestion significantly impacts on the bioactivity and composition of seaweed homogenates. The Irish seaweed species were shown to have anti-proliferative, anti-genotoxic and anti-metastatic activity in in vitro models of colorectal cancer, however pro-inflammatory activity of digested treatments was also observed.

Thesis is embargoed until  31st August 2016

Date of Award	Aug 2014
Original language	English
Sponsors	Marine Institute, Ireland
Supervisor	Chris Gill (Supervisor), Emeir McSorley (Supervisor) & Pamela Magee (Supervisor)