Structure-activity relationships of acid-hydrolyzed Carrageenans: Molecular modifications and anticancer activity in...

Carrageenans are sulfated polysaccharides found in algae and certain plants, and are widely used in the food industry. By modifying their chemical structures through sulfation, polysaccharides can enhance their biological properties, including anticancer effects. Investigating the relationship between carrageenan structure and biological effects is essential to understanding how carrageenans may affect cancer cells. We chemically modified carrageenans by acid hydrolysis, evaluated their biological effects on colon cancer cells, and characterized their molecular structure. HPSEC-RID confirmed a decrease in molecular weight and polydispersity of carrageenans. Modified carrageenans decreased cell viability in a lineage-specific manner, distinct from that of the same non-modified ones. A- and B-mod carrageenan samples reduced cellular proliferation and increased p21 protein levels in a p53-independent manner, and B-mod increased the sub-G1 phase of HCT116 cells. FTIR and NMR structural analyses identified β-Gal4SO₄ and 3,6-anhydro-α-Gal (DA) units in the A-mod sample; β-Gal4SO₄ and 3,6-anhydro-α-Gal2SO₄ units, and also DA units, resulting from a specific desulfation reaction at the 2-position of 3,6-anhydro-α-Gal, in the B-mod sample. Since B-mod showed higher-molecular-weight fragments and fewer low-molecular-weight fragments, it indicates greater potential for in vitro anticancer activity and requires further optimization for safer use.