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The effect of selenium compounds on extracellular redox modulating capacity was studied in murine macrophage RAW 264.7 cells and differentiated human THP-1 monocytes. The arylselenium compounds benzeneselenol (PhSeH), dibenzyl diselenide (DBDSe), diphenyl diselenide (DPDSe), and ebselen were capable of inducing extracellular cysteine accumulation via a cystine- and glucose-dependent process. Extracellular cysteine production was dose-dependently inhibited by glutamate, an inhibitor of cystine/glutamate antiporter (Xc(-) transporter), supporting the involvement of Xc(-) transporter for cystine uptake in the above process. These arylselenium compounds also induced cellular thioredoxin reductase (TrxR) expression, particularly at the exofacial surface of cells. TrxR1 knockdown using small interfering RNA attenuated TrxR increases and cysteine efflux induced in cells by DPDSe. Sodium selenite (Na2SeO3), selenomethionine (SeMet), seleno-l-cystine (SeCySS), and Se-methylselenocysteine (MeSeCys) did not have these effects on macrophages under the same treatment conditions. The effects of organoselenium compounds on extracellular redox may contribute to the known, but inadequately understood, biological effects of selenium compounds.

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Morinda citrifolia (noni) fruit is a well-recognised natural product that reportedly has a broad range of immune enhancing effects (1) . Although several classes of metabolites have been described, few studies have evaluated the effects of compounds isolated from noni fruit on immune function (2) . Of particular interests were two classes of compounds, coumarins and flavanoids. Scopoletin is a pharmacologically active coumarin compound, which has been isolated from noni fruit. Reagent grade scopoletin inhibits the production of inflammatory cytokines. Flavanoids, including rutin, which is in noni, and quercetin, which is the aglycon form of rutin, have recognised antioxidant, anti-inflammatory and antineoplastic properties. The objective of this study was to investigate the dose response of two extraction fractions from noni puree, containing scopoletin and flavanoid compounds, on nitric oxide induction in RAW cells and cell viability in prostatic cancer (PC3) cells. Cell viability was quantified by Calcein AM, MTT and propidium iodide (PI) staining assays. Noni powder was extracted with ethyl acetate (EA) for compound isolation. The crude extract was fractionated using flash column chromatography with 30 % acetone/hexane to obtain four fractions and F3 was identified as scopoletin. Fraction F4 was fractionated further using reversed-phase TLC with 50 % acetone/water to obtain 5 fractions (F4.1, F4.3, F4.4, F4.5 and F4.6). F4.4 was identified as flavonoid-like compound (Fig. 1) These preliminary studies demonstrate that scopoletin and flavanoid rich fractions from noni puree inhibited NO production and PC3 cell growth. Further investigations of the mechanism by which different noni compounds singularly or in combination modulate cancer growth is underway.