Chemopreventive effects of the standardized extract (DA-9601) of Artemisia asiatica on azoxymethane-initiated and dextran sulfate sodium-promoted mouse colon carcinogenesis.
Dextran sulfate sodium (DSS) administration has been reported to cause inflammation in mouse colonic mucosa, which promotes colon carcinogenesis. When male ICR mice were treated with a single intraperitoneal dose (10 mg/kg body weight) of azoxymethane (AOM) followed by 2.5% DSS in drinking water for 7 consecutive days, all developed tumors at the 16th wk, mostly in the distal colon. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were markedly upregulated in the AOM-initiated and DSS-promoted colon tumors. The DNA binding activity of nuclear factor-kappaB (NF-kappa B) was also elevated in the colon tumors. In this study, we examined the chemopreventive effects of the standardized extract (DA-9601) of Artemisia asiatica that has been used in the traditional herbal medicine for the treatment of inflammatory disorders. Mice fed the chow diet containing 10% DA-9601 for 15 wk following DSS treatment displayed the significantly lower multiplicity of colon tumors. DA-9601 treatment suppressed the expression of COX-2 and iNOS as well as NF-kappa B DNA binding in the colonic tissues. It also downregulated the phosphorylation of extracellular, signal-regulated protein kinase and p38 mitogen-activated protein kinase that are upstream of NF-kappa B. Furthermore, DA-9601 reduced expression of beta-catenin in colonic mucosa of mice challenged with AOM plus DSS.
Kim
Hyun Soo
HS
Seoul National University, Seoul, South Korea.
Kundu
Joydeb Kumar
JK
Lee
Jeong-Sang
JS
Oh
Tae-Young
TY
Na
Hye-Kyung
HK
Surh
Young-Joon
YJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D019306:Artemisia; D001397:Azoxymethane / Q000633:toxicity; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000032:analysis; D004247:DNA / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D010936:Plant Extracts / Q000494:pharmacology*; D051176:beta Catenin / Q000235:genetics
D016588:Anticarcinogenic Agents; C116959:DA 9601; D016328:NF-kappa B; D010936:Plant Extracts; D051176:beta Catenin; D004247:DNA; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001397:Azoxymethane