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Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)
Published on: September 11, 2012
Anti-mutagenic lichen extract has double-edged effect on azoxymethane-induced colorectal oncogenesis in C57BL/6J mice
Xiaoqiong He1, Ying Hu, Jean Winter
1Institute of Nutrition and Food Science, School of Public Health, Kunming Medical College, Yunnan 650031, PR China. hexqcn@yahoo.com.cn
Abstract:
This study compared the effects of three anti-mutagenic lichen extracts on colorectal oncogenesis in azoxymethane (AOM)-treated mice and determined whether the extracts also regulated the homeostatic response to genotoxic damage. C57BL/6J mice (n = 12 per group) were treated with the lichen extracts Antimutagen-He (AMH): AMH-C, AMH-D, or AMH-E dimethyl sulfoxide (DMSO, control) for 2 weeks. At the end of the treatment, mice were given a single AOM injection to induce DNA damage and killed 6 h later for measuring apoptosis and proliferation. Apoptotic and proliferation indexes in mice treated with AMH-C, AMH-D, and AMH-E were 0.61%, 1.41%, and 0.77%; and 30.62%, 21.93%, and 27.27%, respectively, which were significantly lower than those of control mice (5.88% and 38.69%) (p < 0.05). To examine the effects of lichen extracts on colorectal cancer, separate groups of mice (n = 25 per group) treated with AMH-C, AMH-D, AMH-E, or DMSO were given 4-weekly AOM injections to induce oncogenesis. Mice were killed 24 weeks after the last AOM injection for assessing colon tumor formation. Colonic tumor incidences were 47.3%, 13%, and 20%; the tumor volumes were 18.47, 2.75, and 10.78 mm(3), respectively, in mice treated with AMH-C (p < 0.05), AMH-D (p < 0.05), and AMH-E (p > 0.05), compared to 24% and 13.28 mm(3) in mice of control correspondingly. No lichen extract showed evident toxic effects on mice. No usnic acid was found in these lichen extracts. The regulation of acute apoptosis and cell proliferation in colonic epithelial cells and the anti-mutagenesis do not seem directly related to the cancer protective effect.
Insights
Three lichen extracts (AMH-C, AMH-D, AMH-E) significantly reduced colorectal cancer in mice. These extracts, derived from Antimutagen-He, showed anti-mutagenic properties without causing toxicity.
Area of Science:
- * Pharmacology and Toxicology
- * Cancer Research
- * Natural Product Chemistry
Background:
- * Colorectal cancer (CRC) poses a significant global health challenge.
- * Investigating natural compounds for chemoprevention is crucial.
- * Lichen extracts are explored for their potential anti-mutagenic and anti-cancer properties.
Purpose of the Study:
- * To evaluate the anti-cancer effects of three lichen extracts (AMH-C, AMH-D, AMH-E) from Antimutagen-He on azoxymethane-induced colorectal oncogenesis in mice.
- * To determine if these extracts modulate the homeostatic response to genotoxic damage, including apoptosis and cell proliferation.
- * To assess the safety and potential toxicity of the lichen extracts.
Main Methods:
- * C57BL/6J mice were treated with lichen extracts or DMSO (control).
- * Acute genotoxicity was induced with a single azoxymethane (AOM) injection; apoptosis and proliferation were measured.
- * Chronic oncogenesis was induced with weekly AOM injections; tumor incidence and volume were assessed after 24 weeks.
Main Results:
- * Lichen extracts significantly reduced apoptosis and proliferation in colonic epithelial cells compared to controls (p < 0.05).
- * AMH-C and AMH-D treatments markedly decreased colorectal tumor incidence and volume (p < 0.05).
- * No significant toxic effects were observed with any lichen extract; usnic acid was absent.
Conclusions:
- * Lichen extracts AMH-C and AMH-D demonstrate significant chemopreventive effects against colorectal cancer in a mouse model.
- * The anti-mutagenic and homeostatic regulatory effects do not appear to be directly linked to the observed cancer-protective mechanisms.
- * Further research is warranted to elucidate the specific compounds and pathways responsible for the anti-cancer activity of these lichen extracts.
