Anti-tumor activity of an enzymatically synthesized alpha-1,6 branched alpha-1,4-glucan, glycogen.
Oral administration of an enzymatically synthesized alpha-1,4:1,6-glycogen (ESG) at a dose of 50 mug/ml significantly prolonged the survival time of Meth A tumor-bearing mice. ESG also significantly stimulated macrophage-like cells (J774.1), leading to augmented production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). The weight-average degree of polymerization (DPw) and the ratio of branch linkage (BL) of ESG were 149,000 and 8.1% respectively. beta-Amylase-treated ESG, however, lost J774.1-activating activity although inhibited subcutaneous growth of Meth A tumor cells admixed with it. Its DPw and BL changed to 126,000 and 20% respectively. Partially degraded amylopectin [(AP), DPw: 110,000, BL; 5.1] was also effective at stimulating J774.1, but its activity was lower than that of ESG. Other alpha-glucans [cycloamylose (CA), enzymatically synthesized amylose (ESA), highly branched cyclic dextrin (HBCD), and beta-amylase-treated HBCD], of which DPw was lower than that of ESG, showed no J774.1-activating activity and weaker anti-tumor activity.
Ryoyama
Kazuo
K
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Aomori University, Japan. ryoyama@amori-u.ac.jp
Kidachi
Yumi
Y
Yamaguchi
Hideaki
H
Kajiura
Hideki
H
Takata
Hiroki
H
D000688:Amylose / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D005936:Glucans / Q000737:chemistry; D006003:Glycogen / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D005936:Glucans; D007202:Indicators and Reagents; D013778:Tetrazolium Salts; D013844:Thiazoles; D009569:Nitric Oxide; D006003:Glycogen; D000688:Amylose; C022616:thiazolyl blue