4.7 Article

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

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MARINE DRUGS
卷 20, 期 12, 页码 -

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MDPI
DOI: 10.3390/md20120741

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antitumor activity; oligosaccharides; carrageenans; Chondrus armatus; colon cancer; esophageal carcinoma; cell cycle

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In this study, kappa o- and lambda o- oligosaccharides from the marine algae Chondrus armatus were isolated, purified and structurally characterized. The tumor suppressive activity of these carrageenans was examined in gastrointestinal cancer models, showing pronounced antiproliferative effects and cell cycle inhibition in cancer cells. Furthermore, the carrageenans induced apoptosis in adenocarcinomas. These results highlight the potential of kappa o- and lambda o- carrageenans for drug development in colon and esophageal carcinoma.
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.

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