Anti-tumor-promoting activities of agaro-oligosaccharides on two-stage mouse skin carcinogenesis.
We have previously reported that agaro-oligosaccharides (AGOs) suppressed the elevated levels of nitric oxide (NO), prostaglandin E₂(PGE₂), and pro-inflammatory cytokines in activated monocytes/macrophages, via heme oxygenase-1 induction. In this report, we initially demonstrated that AGOs intake inhibited NO production in activated peritoneal macrophages. Then, we tested for the ability of AGOs to prevent tumor promotion on the two-stage mouse skin carcinogenesis model. As a result, AGOs feeding led to delayed tumor appearance and decreased tumor number. It is known that PGE₂ is one of key players in carcinogenesis. Thus, we confirmed that PGE₂ production was suppressed by AGOs intake in TPA-induced ear edema model. We also demonstrated that cyclooxygenase-2 and microsomal PGE synthase-1, rate-limiting enzymes in PGE₂ production, were down-regulated by AGOs in human monocytes. Consequently, AGOs are expected to prevent tumor promotion by inhibiting PGE₂ elevation in chronic inflammation site.
Biotechnology Research Laboratories, Takara Bio Inc., Shiga 520-2193, Japan. enokit@takara-bio.co.jp
Tatsuji
T
Enoki
Takanari
T
Tominaga
Fuyuko
F
Takashima
Hiromu
H
Ohnogi
Hiroaki
H
Sagawa
Ikunoshin
I
Kato
D015127:9,10-Dimethyl-1,2-benzanthracene; D000362:Agar; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002273:Carcinogens; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D013755:Tetradecanoylphorbol Acetate
D000970:Antineoplastic Agents; D002273:Carcinogens; D009573:Nitrites; D009844:Oligosaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D015127:9,10-Dimethyl-1,2-benzanthracene; D000362:Agar; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate