κ- and λ-Carrageenans from Marine Alga Chondrus armatus Exhibit Anticancer In Vitro Activity in Human Gastrointestinal Cancers Models

The carrageenans isolated from red algae demonstrated a variety of activities from antiviral and immunomodulatory to antitumor. The diverse structure and sulfation profile of carrageenans provide a great landscape for drug development. In this study, we isolated, purified and structurally characterized kappa o- and lambda o- oligosaccharides from the marine algae Chondrus armatus. We further examined the tumor suppressive activity of both carrageenans in gastrointestinal cancer models. Thus, using MTT assay, we could demonstrate a pronounced antiproliferative effect of the carrageenans in KYSE-30 and FLO-1 as well as HCT-116 and RKO cell lines with IC50 184 similar to 405 mu g/mL, while both compounds were less active in non-cancer epithelial cells RPE-1. This effect was stipulated by the inhibition of cell cycle progression in the cancer cells. Specifically, flow cytometry revealed an S phase delay in FLO-1 and HCT-116 cells under kappa o-carrageenan treatment, while KYSE-30 demonstrated a pronounced G(2)/M cell cycle delay. In line with this, western blotting revealed a reduction of cell cycle markers CDK2 and E2F2. Interestingly, kappa o-carrageenan inhibited cell cycle progression of RKO cells in G(1) phase. Finally, isolated kappa o- and lambda o- carrageenans induced apoptosis on adenocarcinomas, specifically with high apoptosis induction in RKO cells. Overall, our data underline the potential of kappa o- and lambda o- carrageenans for colon and esophageal carcinoma drug development.