Anti-angiogenic and anti-metastatic effects of beta-1,3-D-glucan purified from Hanabiratake, Sparassis crispa.
Sparassis crispa (SC), Hanabiratake in Japanese, is an edible mushroom with medicinal properties, that contains more than 40% beta-D-glucan. It was concluded from results of the methylation study that beta-D-glucan from SC (SBG) was composed of a backbone of beta-(1-->3)-linked D-glucopyranosyl residues, and had beta-D-glucopyranosyl groups joined through O-6 and O-2 of D-glucose of the backbone. We purified SBG and investigated its anti-angiogenic functions and anti-metastatic effects on neoplasm using different animal models. The oral administration of the purified SBG suppressed B16-F10 cell-induced angiogenesis in the dorsal air sac assay using female ICR mice as well as vascular endothelial growth factor induced neovascularization in the Matrigel plug assay using female C57BL/6J mice. Furthermore, it suppressed the growth and numbers of the metastatic tumor foci in lung, along with the primary tumor growth in the spontaneous metastatic model using female C57BL/6J mice. From these results, it is apparent that the oral administration of SBG results in suppressive effect on tumor growth and metastasis in lung through the inhibition of tumor induced-angiogenesis. These effects are not a result of direct action on the endothelial cells because cell growth, migration and capillary-like tube formation were not affected in the human umbilical vein endothelial cells by SBG application. This is the first report showing that the oral administration of SBG is capable of suppressing angiogenesis and metastasis.
Yamamoto
Kyosuke
K
Research & Development Center, Unitika Ltd., Uji, Kyoto, Japan. kyosuke-yamamoto@unitika.co.jp
Kimura
Takashi
T
Sugitachi
Akio
A
Matsuura
Nariaki
N
D000363:Agaricales / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology; D008745:Methylation; D051379:Mice; D008813:Mice, Inbred ICR; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D011509:Proteoglycans; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D047071:beta-Glucans / Q000302:isolation & purification / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D047071:beta-Glucans; C010770:polysaccharide-K