Colon cancer is the third most common cancer and the second leading cause of cancer-related death in the United States, emphasizing the need for the discovery of new cellular targets. Using a metabolomics approach, we report here that epoxygenated fatty acids (EpFA), which are eicosanoid metabolites produced by cytochrome P450 (CYP) monooxygenases, were increased in both the plasma and colon of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer mice. CYP monooxygenases were overexpressed in colon tumor tissues and colon cancer cells. Pharmacologic inhibition or genetic ablation of CYP monooxygenases suppressed AOM/DSS-induced colon tumorigenesis in vivo. In addition, treatment with 12,13-epoxyoctadecenoic acid (EpOME), which is a metabolite of CYP monooxygenase produced from linoleic acid, increased cytokine production and JNK phosphorylation in vitro and exacerbated AOM/DSS-induced colon tumorigenesis in vivo.Together, these results demonstrate that the previously unappreciated CYP monooxygenase pathway is upregulated in colon cancer, contributes to its pathogenesis, and could be therapeutically explored for preventing or treating colon cancer.Significance: This study finds that the previously unappreciated CYP monooxygenase eicosanoid pathway is deregulated in colon cancer and contributes to colon tumorigenesis. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): Figure 4. EpOME exaggerates AOM/DSS-induced colon tumorigenesis in vivo. A, Scheme of animal experiment to test the effect of 12,13-EpOME (dose, 2 mg/kg/day; administered via mini-pump) on colon tumorigenesis. B, Quantification of colon tumorigenesis in mice (n ¼ 8-9 per group). C, Expression of proinflammatory and protumorigenic genes in colon (n ¼ 6-8 per group). D, Quantification of CD45 þ and CD45 þ F4/80 þ immune cells in colon (n ¼ 7-8 per group). E, Hematoxylin and eosin (H&E) histology and IHC staining of PCNA and b-catenin in colon (n ¼ 6-7 per group; scale bar, 50 mm). The results are expressed as mean AE SEM. The statistical significance of two groups was determined using Student t test or Wilcoxon-Mann test.
The dissociation constants (pK a ) of daidzein and genistein were determined at 298.2 K by ultraviolet (UV) spectroscopy method. The pK a1 and pK a2 values of daidzein are 7.51 ± 0.07 and 9.47 ± 0.14 and ones of genistein are 7.25 ± 0.84 and 9.53 ± 0.15, respectively. The solubilities of daidzein and genistein in water, methanol, ethyl ethanoate, propanone, trichloromethane, and hexane have been measured using UV spectrophotometric method from (288.2 to 328.2) K at atmospheric pressure. The solubilities of daidzein and genistein in all solvents increase with an increase in temperature. The solubility of daidzein in the six solvents was in the order propanone > methanol > ethyl ethanoate > hexane > trichloromethane > water, whereas the solubility order of genistein was propanone > ethyl ethanoate > methanol > hexane > trichloromethane > water. In comparing the solubility of genistein with that of daidzein, the 5-hydroxyl group of genistein causes a significantly higher solubility in methanol and ethyl ethanoate, a little higher solubility in trichloromethane (exception 328.2 K), an approximately equivalent solubility in water, and a slightly lower solubility in propanone. The measured solubility data were correlated with a modified Apelblat equation, λh model, and ideal model. From solubility of daidzein and genistein in these six solvents, the dissolution enthalpy, entropy, and change of the free Gibbs energy were evaluated using the van't Hoff equation.
Soybean [Glycine max (Linn.) Merrill] and mung bean [Vigna radiate (Linn.) Wilczek] plants were challenged with 5 kinds of heavy metals [cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb) and mercury (Hg)] in a hydroponic system. We applied 4 different metal treatments to study the effects of heavy metals on several physiological and biochemical parameters in these species, including root length, heavy metal concentrations and allocation in different organs, superoxide dismutase, catalase, and peroxidase activities, the content of malondialdehyde (MDA), protein and chlorophyll. The data showed that the growth of the roots of soybean and mung bean was equally sensitive to external Hg concentrations. Soybean was more sensitive to external Cd concentrations, and mung bean was more sensitive to external Cr, Cu and Pb concentrations. Normal concentrations of heavy metal would not cause visible toxic symptoms, and a low level of heavy metal even slightly stimulated the growth of plants. With the rise of heavy metal concentration, heavy metal stress induces an oxidative stress response in soybean and mung bean plants, characterized by an accumulation of MDA and the alternation pattern of antioxidative enzymes. Meanwhile, the growth of plants was suppressed, the content of chlorophyll decreased and leaves showed chlorosis symptoms at high metal concentrations.
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