Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in Apc^Min/+ Mice

Abstract

American ginseng (Panax quinquefolius L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered ApcMin/+ mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the ApcMin/+ mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids and carbohydrates were observed in ApcMin/+ mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the ApcMin/+ induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms.

Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model

“…A recent CE-TOFMS-based metabolomics study suggested that the metabolic profile of DEN model is effective to identify novel biomarkers for early diagnosis of human hepatocellular carcinoma (30). Indeed, inhibition of AA metabolic pathway has been recently reported to associate with the chemoprevention of high fat diet-enhanced colorectal carcinogenesis (41) and the apoptosis of hepatocellular carcinoma cells (42). Furthermore, significantly elevated content of AA was also reported in hepatocellular carcinoma patients compared with the healthy controls (11).…”

American Ginseng Attenuates Colitis-Associated Colon Carcinogenesis in Mice: Impact on Gut Microbiota and Metabolomics

“…Quantitative real-time PCR was performed on a 7900HT RT-qPCR system (Applied Biosystems, Foster City, CA). The primers used for real-time PCR were described previously (24, 25). β -actin was used as an endogenous control.…”

“…The levels of cytokines IL-1β and IL-6 were quantified by ELISA (Life Technologies, Grand Island, NY) (24). …”

“…Serum and stool samples were pretreated with different solvents and derivatization reagents (24, 26). GC/MS analyses were performed on an Agilent 7890N gas chromatograph coupled with a Pegasus HT time-of-flight mass spectrometer (Leco Corporation, St Joseph, MI) (24).…”

“…GC/MS analyses were performed on an Agilent 7890N gas chromatograph coupled with a Pegasus HT time-of-flight mass spectrometer (Leco Corporation, St Joseph, MI) (24). Metabolomic data were analyzed using principle component analysis (PCA).…”