Studies on interrelation of structure and antitumor effects of polysaccharides: antitumor action of periodate-modified, branched (1 goes to 3)-beta-D-glucan of Auricularia auricula-judae, and other polysaccharides containing (1 goes to 3)-glycosidic linkages.
Antitumor activities of two (1 goes to 3)-beta-D-glucans, isolated from the fruiting body of Auricularia auricula-judae ("kikurage", an edible mushroom), and other branched polysaccharides containing a backbone chain of (1 goes to 2)-alpha-D-glucosidic or (1 goes to 3)-alpha-D-mannosidic linkage [and their corresponding (1 goes to 3)-D-glycans, derived by mild, Smith degradation] were compared. Among these polysaccharides, a water-soluble, branched (1 goes to 3)-beta-D-glucan (glucan I) of A. auricula-judae exhibited potent, inhibitory activity against implanted Sarcoma 180 solid tumor in mice. The alkali-insoluble, branched (1 goes to 3)-beta-D-glucan (glucan II), a major constituent of the fruiting body, showed essentially no inhibitory activity. When the latter glucan, having numerous branches attached, was modified by controlled, periodate oxidation, borohydride reduction, and mild, acid hydrolysis, the resulting, water-soluble, regraded glucan, having covalently linked polyhydroxy groups attached at O-6 of the (1 goes to 3)-linked D-glucosyl residues, exhibited potent antitumor activity. Further investigations using the glucan-polyalcohol indicated that the attachment of the polyhydroxy groups to the (1 goes to 3)-beta-D-glucan backbone may enhance the antitumor potency of the glucan. On the other hand, partial introduction of carboxymethyl groups into glucan II (d.s., 0.47--0.86), which altered the insolubility property, failed to enhance the antitumor activity. The interrelation between the antitumor activity and the structure of the branched (1 goes to 3)-beta-D-glucan is discussed, on the basis of methylation and 13C-n.m.r. studies of the periodate-modified glucans.
D000818:Animals; D000970:Antineoplastic Agents; D001487:Basidiomycota; D002236:Carbohydrate Conformation; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010946:Plants, Medicinal; D011134:Polysaccharides / Q000302:isolation & purification / Q000627:therapeutic use*; D012510:Sarcoma 180 / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011134:Polysaccharides