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Published on: December 19, 2019
Anti-tumor-promoting activities of agaro-oligosaccharides on two-stage mouse skin carcinogenesis
Tatsuji Enoki1, Takanari Tominaga, Fuyuko Takashima
1Biotechnology Research Laboratories, Takara Bio Inc., Shiga 520-2193, Japan. enokit@takara-bio.co.jp
Abstract:
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.
Insights
Agaro-oligosaccharides (AGOs) inhibit nitric oxide (NO) and prostaglandin E₂ (PGE₂) production, key factors in inflammation and tumor promotion. AGOs feeding delayed tumor appearance and reduced tumor numbers in a mouse skin carcinogenesis model.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Agaro-oligosaccharides (AGOs) have previously shown to suppress pro-inflammatory mediators.
- Nitric oxide (NO) and prostaglandin E₂ (PGE₂) are implicated in inflammatory processes and carcinogenesis.
Purpose of the Study:
- To investigate the anti-tumor promotion effects of AGOs.
- To determine AGOs' impact on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in vivo and in vitro.
Main Methods:
- Assessing NO production in activated peritoneal macrophages following AGOs intake.
- Evaluating AGOs' efficacy in preventing tumor promotion using a two-stage mouse skin carcinogenesis model.
- Measuring PGE₂ levels in a TPA-induced ear edema model and analyzing the expression of key enzymes (cyclooxygenase-2, microsomal PGE synthase-1) in human monocytes.
Main Results:
- AGOs intake inhibited NO production in activated peritoneal macrophages.
- AGOs feeding resulted in delayed tumor appearance and a reduced number of tumors.
- PGE₂ production was suppressed by AGOs in the TPA-induced ear edema model.
- Cyclooxygenase-2 and microsomal PGE synthase-1 were down-regulated by AGOs in human monocytes.
Conclusions:
- AGOs demonstrate potential in preventing tumor promotion.
- The anti-tumor promotion effects of AGOs are likely mediated by the inhibition of PGE₂ elevation in chronic inflammation sites.
