Synthesis and antitumor activities of mitomycin C (1----3)-beta-D-glucan conjugate.
The conjugate of mitomycin C (MMC) with linear (1----3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 was synthesized and its antitumor activities investigated. The conjugate (MMC-carboxymethylated linear (1----3)-beta-D-glucan (CMPS)) was obtained by treatment of CMPS with MMC in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. In vitro cytotoxicity of MMC-CMPS against L1210 leukemia cells was similar to that of MMC. In i.p.-i.p. system in vivo against P388 leukemia in mice, the maximum increase of MMC-CMPS conjugate in life span (ILSmax) was higher than that of MMC but the therapeutic index was reduced. However, the antitumor activity of MMC-CMPS conjugate against subcutaneously implanted sarcoma 180 solid tumor in mice by i.p. administration was similar to that of MMC at a dose of 1.5 mg eq MMC/kg/d x 7 and the reduction of the number of leukocytes caused by MMC was suppressed by attaching MMC to CMPS. In addition, on assay using serum of sarcoma 180 solid tumor-bearing mice with injection of MMC-CMPS conjugate, a drastic loss of tumor cells and an increase in polymorphonuclear leukocytes (PMN) were observed. This result suggested that MMC-CMPS conjugate induced tumor-regressing factor similar to CMPS.
Nagai
K
K
Gifu Pharmaceutical University, Japan.
Tanaka
J
J
Kiho
T
T
Ukai
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D005936:Glucans / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D016685:Mitomycin / Q000138:chemical synthesis* / Q000494:pharmacology; D047071:beta-Glucans
D000970:Antineoplastic Agents; D005936:Glucans; D047071:beta-Glucans; D016685:Mitomycin; C033363:beta-1,3-glucan