Hydrogen peroxide generated by xanthine/xanthine oxidase system represses the proliferation of colorectal cancer cell line Caco-2.

The twin character of reactive oxygen species is substantiated by a growing body of evidence that reactive oxygen species within cells act as inducers and accelerators of the oncogenic phenotype of cancer cells, while reactive oxygen species can also induce cancer cell death and can therefore function as anti-tumorigenic species. The aim of this study was to assess a possible influence of xanthine/xanthine oxidase on the proliferation of colorectal cancer cell line Caco-2. xanthine/xanthine oxidase (2.5 µM/0.25 mU/ml-25 µM/2.5 mU/ml) dose-dependently inhibited the proliferation of Caco-2 cells. Experiments utilizing reactive oxygen species scavengers (superoxide dismutase, catalase and mannitol) and exogenous hydrogen peroxide revealed a major role of hydrogen peroxide in the xanthine/xanthine oxidase effect. Investigations utilizing annexin V-fluorescein/PI assay using flow cytometry, and the lactate dehydrogenase extracellular release assay indicated that hydrogen peroxide induced necrosis, but not apoptosis, in Caco-2 cells. These results suggest that hydrogen peroxide generated by xanthine/xanthine oxidase has the potential to suppress colorectal cancer cell proliferation.

Monochloramine suppresses the proliferation of colorectal cancer cell line Caco-2 by both apoptosis and G2/M cell cycle arrest.

The aim of this study was to assess a possible role of monochloramine (NH2 Cl), one of the reactive chlorine species, which induce oxidative stress, on the proliferation of colorectal cancer cell line Caco-2. At concentrations ranging from 10 to 200 µM, NH2 Cl (14-61% inhibition), but not hypochlorous acid, dose-dependently inhibited the cell viability of Caco-2 cells. Experiments utilizing methionine (a scavenger of NH2 Cl), taurine-chloramine and glutamine-chloramine revealed that only NH2 Cl affects the cancer cell proliferation among reactive chlorine species, with a relative specificity. Furthermore, flow-cytometry experiments showed that the anti-proliferative effect of NH2 Cl is partially attributable to both apoptosis and G2/M cell cycle arrest. These results suggest that NH2 Cl has the potential to suppress colorectal cancer cell proliferation.

Perfluorinated carboxylic acids inhibit cyclooxygenase pathway more potently than 12-lipoxygenase pathway in rat platelets.

Two perfluorinated carboxylic acids (PFCAs), pentadecafluorooctanoic acid (PDFOA) and heptadecafluorononanoic acid (HDFNA), were investigated for potential modulatory effects on the cyclooxygenase (COX) and 12-lipoxygenase (LOX) metabolisms in rat platelets. Both PDFOA and HDFNA dose-dependently inhibited the formation of a COX metabolite, 12-HHT, without any effect on that of a LOX metabolite, 12-HETE, at concentrations ranging from 10 to 100µM. These two PFCAs up to 100µM did not affect platelet membrane integrity, and COX-1 and -2 protein expression levels in Caco-2 cells. These results suggest that PDFOA and HDFNA have the potential to modify platelet function by inhibiting the COX pathway at activity level, but not at protein level.

Selenite induces oxidative DNA damage in primary rat hepatocyte cultures.

The effects of selenite ions on oxidative DNA damage in primary rat hepatocyte cultures were examined. Selenite ions dose-dependently stimulated 8-hydroxydeoxyguanosine formation in DNA from the hepatocyte cultures at concentrations of 1, 5 and 10 micromol/L (1.6-, 2.5- and 3.6-fold). Selenite ions also induced DNA fragmentation in nucleus from the hepatocyte cultures at concentrations of 5 and 10 micromol/L. Selenite ions could not affect protein expression levels of 8-oxoguanine DNA glycosylase 1 which is responsible for excision of 8-hydroxydeoxyguanosine from DNA, but could increase 2',7'-dichlorofluorescein-fluorescence intensity from 2',7'-dichlorodihydrofluorescein, an indicator of reactive oxygen species generation, at concentrations of 5 and 10 micromol/L. Furthermore, an increase in 8-hydroxydeoxyguanosine induced by selenite ions (10 micromol/L) was inhibited by free radical scavengers (alpha-tocopherol, N-acetyl-L-cysteine, and melatonin) at concentrations more than 50 micromol/L. These observations imply that selenite ions have the potential to induce oxidative DNA damage in the liver through an increase in reactive oxygen species formation, but not a decrease in 8-oxoguanine DNA glycosylase 1 protein expression levels.