246

Inhibitory Effects of Agaro-oligosaccharides on NO and PGE2 Generation in Acti vated -Macrophages

ENOKI Tatsuji1, TOMINAGA Takanari1, SAGAWA Hiroaki1, KATO Ikunoshinl (Biotech. Res. Lab., Takara Shuzo Co., Ltd.)

(Purpose) Agaro-oligosaccharides produced by decomposing agarose, a main element of agarhas inhibitory effects on LPS-induced NO generation in mouse macrophages I). This time, we studied in detail inhibitory effects on NO generation by agaro- oligosaccharides and also investigated inhibitory ~ffects on ProstaglandinE2 (PGE2) generation induced by TPA as a cancerogenic promoter as weIl as LPS.

(Results) Agaro-oligosaccharides successfully inhibited LPS.IFNy-induced NO generation depending on concentration in mouse macrophages cell line RAW264. 7. In a division added by agaro-oligosaccharides, inhibitory effects were confirmed at the mRNA level of iNOS which is induced-NO synthase. ln addition, agaro- oligosaccharides show inhibitory effects on PGE2 generation induced by LPS or TPA in the same cell. The inhibitory effects on PGE2 generation are now being studied in detail.

(Conclusion) Agaro-oligosaccharides have inhibitory effects on NO and PGE2 generation of inflammation mediator induced by LPS and TPA, so that their possibility was suggested as a preventive food for cancerogenic substance.

1) 57th Japan Cancer Society General Congress Proccelings

248

Anti-Inflammatory Action of Agaro-Oligosaccarides on TPA-Induced Inflammation in 1Mice
TOMINAGA Takanari1, NISHIYAMA Eiji1, ENOKI Tatsuji1, SAGAWA Hiroaki1, MIZUTANI Shigetoshi1, KATO Ikunoshin1 (Biotech. Res. Lab., Takara Shuzo Co., Ltd.)

(Purpose) At the conference last year, we reported that agaro-oligosaccarides produced from hydrolysis of agarose, main element of agar suppress NO generation from mice macrophages cellline RAW264.7 stimulated by LPS in vitro. This time, we studied related actions administrated to mice using TPA inflammation model as a cancerogenic promoter.

(Results) NO or PGE2 generations induced by LPS or TPA in mouse peritoneal macrophage were suppressed by water drinking of agaro-oligosaccarides. ln TPA induced mouse auri-edema model, it was observed that PGE2 generation at edema suppression or inflammatory region was reduced.

(Discussion) We have confirmed that possibility of agaro-oligosaccarides to suppress cancerogenic action by limiting separation of inflammatory mediator due to cancerogenic substance. At present, we are studying this effect at two stages of TPA induced cancerogenic model, which will be reported as weIl.

2258

Anti-tumor Activity of Oligosaccharides from Agar against Human Colon Cancer Xenografts

YU Fu-gong1, SAKAI Takeshi1, KATO Ikunoshinl (Biotech Res. Lab., Takara Shuzo Co., Ltd.)

(Purpose) Last year, we reported that agaro-oligosaccharides have tendency to induce apoptosis of HL-60 cell and suppress NO generation in LPS-induced macrophages ( 1 ). This time, we studied safety for agaro-oligosaccharides orally administrated and its resultant anti-cancer action.

(Method) (I) Three percent of agaro-oligosaccharides was orally administrated to regular ICR mice (five mice per group) for 32 weeks, then whose individual organs were extracted for comparison with data for non-administrated group. (II) Human colon cancer cellline HCT 116 was transplanted under the skin of nude mice (ten mice per group) to generate tumor, then three percent of agaro-oligosaccharides was administrated as drinking water for four weeks to measure changes in tumor's sizes with time.

(Results) (I) There is no influence found due to agaro-oligosaccharides orally administrated in each organ of the regular mice. (Il) Tumors for non-administrated group increased by 17 times compared with initial sample, while those for agaro- oligosaccharides administered group increased by five times. For the agaro- oligosaccharides administrated group with highest anti-tumor effect, the tumor disappeared in two weeks after administration.

(Discussion) These results show that agro-oligosaccarides if orally administrated will not affect to the regular mice and are effective to supress the tumor in the nude mice with human colon cancer transplanted.

(1) ENOKI, et. Al.: 57th Japan Cancer Society General Congress Proccelings Article, p645,1998