Oxidative degradation of an antitumor (1-3)-beta-D-glucan, grifolan.
A (1-3)-beta-D-glucan, grifolan (GRN), recovered from the peritoneal cavity after 1 d from i.p. injection contained a significant amount of anionic metabolite(s) having lower Mr than the parent GRN. In parallel with this observation, GRN induced peritoneal exudate cells exhibiting a higher level of oxidative burst than the non-stimulated, resident peritoneal cells. Chemical oxidation of GRN by active oxygen species such as (a) ascorbic acid-CuSO4, (b) hydrogen peroxide, (c) hydrogen peroxide-CuSO4, or (d) hypochlorous acid also produced anionic as well as lower Mr degradation products. Under these experimental conditions the structural changes were remarkable and in the order of a less than b less than c less than d. The products formed under the conditions (a) and (b) retained significant antitumor activity but those of (c) and (d) lost the activity. However, oxidation product(s) of curdlan, an antitumor inactive (1-3)-beta-D-glucan having no branch, by condition (d) induced significant antitumor activity. These results suggested that oxidative degradation of (1-3)-beta-D-glucans produced some temporary active metabolites and then gradually changed to the inactive form. However, these active metabolites contribute less than the parent glucan on the whole activation mechanisms of the host by (1-3)-beta-D-glucans.
Nono
I
I
Tokyo College of Pharmacy, Japan.
Ohno
N
N
Masuda
A
A
Oikawa
S
S
Yadomae
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D043326:Glucan 1,3-beta-Glucosidase; D005936:Glucans / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010529:Peritoneal Cavity; D013329:Structure-Activity Relationship; D047071:beta-Glucans; D001617:beta-Glucosidase / Q000302:isolation & purification
D000903:Antibiotics, Antineoplastic; D005936:Glucans; D047071:beta-Glucans; C048444:grifolan; C038459:curdlan; D006861:Hydrogen Peroxide; D001617:beta-Glucosidase; D043326:Glucan 1,3-beta-Glucosidase; D010100:Oxygen