Chemopreventive Effects of the Standardized Extract (DA-9601) of Artemisia asiatica on Azoxymethane-Initiated and Dextran Sulfate Sodium-Promoted Mouse Colon Carcinogenesis

Abstract

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-κ 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-κ 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-κ B. Furthermore, DA-9601 reduced expression of β-catenin in colonic mucosa of mice challenged with AOM plus DSS.

ACKNOWLEDGMENTS

This work was supported by the Institute of the Complementary and Alternative Medicine, Seoul National University and the SRC Program (R11-2007-107-00000-0) for the Innovative Drug Research Center (IDRC) and the National Research Laboratory Fund, Korea Science and Engineering Foundation, Republic of Korea. Joydeb Kumar Kundu is a recipient of Brain Korea (BK)-21 Assistant Professorship. The first two authors (H.-S. Kim and J. K. Kundu) equally contributed to this work.