Dissociation Constants and Solubilities of Dalbergin and Nordalbergin in Different Solvents

The dissociation constants (p<i>K</i>_a) of dalbergin and nordalbergin were measured at 298.2 K using ultraviolet (UV) spectroscopy method. The solubilities of dalbergin and nordalbergin in water, methanol, propanone, ethyl ethanoate, trichloromethane, and hexane have been determined by the UV spectrophotometric method from 283.2 to 308.2 K at atmospheric pressure. The experimental solubility values were correlated with a modified Apelblat equation, λ<i>h</i> model, and ideal model. The p<i>K</i>_a value of dalbergin is 8.91 ± 0.12, and the p<i>K</i>_a1 and p<i>K</i>_a2 values of nordalbergin are 7.31 ± 0.29 and 9.79 ± 0.39, respectively. The solubilities of dalbergin and nordalbergin in six solvents increase with an increase in temperature. The solubility order of dalbergin in six pure solvents was trichloromethane > propanone > ethyl ethanoate > methanol > hexane > water, whereas that of nordalbergin was propanone > methanol > ethyl ethanoate > trichloromethane > water > hexane. A comparison of the solubility of dalbergin with that of nordalbergin shows that the 7-methoxyl moiety of dalbergin leads to a significantly higher solubility in trichloromethane and hexane, a little higher solubility in ethyl ethanoate, an approximately equal solubility in propanone, and a little lower solubility in methanol and water (exception 283.2 K). For dalbergin, the modified Apelblat equation shows the best correlation for all solvents, and for nordalbergin, correlation results by three models are similar

Targeted Metabolomics Identifies the Cytochrome P450 Monooxygenase Eicosanoid Pathway as a Novel Therapeutic Target of Colon Tumorigenesis

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

Targeted metabolomics identifies the cytochrome P450 monooxygenase eicosanoid pathway as a novel therapeutic target of colon tumorigenesis

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