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Age-related changes in calcium metabolism play a role in the development of osteoporosis. A 4-wk feeding study was conducted in 5-mo-old ovariectomized (OVX) Sprague-Dawley rats to assess the effect of various dietary fibers on mineral metabolism and bone health parameters. There were 6 treatment groups: sham-Control, OVX-Control, OVX rats receiving daily estradiol (E2) injections, and OVX rats receiving an AIN-93M diet supplement with either an inulin-based fiber (Synergy1® or Fruitafit HD®) or a novel fiber (polydextrose) at 5% wt. of diet. Calcium and magnesium metabolic balances were performed after early (3 d) and late exposure (4 wk) to dietary treatments. Rats receiving polydextrose had significantly higher net calcium absorption efficiency and retention than all control groups and a trend (P≤ 0.10) for higher calcium absorption when compared to inulin-based fibers after early exposure but the advantage did not persist over long-term exposure. The inulin-based fibers had positive chronic effects on calcium metabolism that were related to changes in the gut, that is, production of short chain fatty acids and higher cecal wall weights. All fibers improved magnesium absorption and retention in early and late metabolic balances; effects on magnesium metabolism were more pronounced than for calcium. Practical Application: Steady growth in US middle-aged and elderly populations has led to higher incidences of several chronic diseases including osteoporosis, a bone disease that primarily affects postmenopausal women. Recent research suggests that certain dietary fibers (prebiotics) enhance mineral absorption and may impart bone health benefits. This work examines the impact of prebiotic supplementation on mineral metabolism and bone health using a postmenopausal rat model. Study findings will aid future investigations in ascertaining the factors related to potential bone health benefits of prebiotic which will aid in developing an effective prebiotics food product/supplement that will address the bone health needs of consumers.

Elevated serum androgens are associated with increased prostate cancer risk. Tomato consumption is also associated with reduced prostate cancer incidence, and the primary tomato carotenoid, lycopene, may modulate androgen activation in the prostate, yet little is known about other tomato carotenoids. To evaluate interrelations between phytofluene, lycopene, or tomato powder consumption and androgen status, 8-wk-old male F344 rats (fed a control AIN 93G diet) were castrated or sham-operated and subsequently provided with daily oral supplementation of phytofluene or lycopene ( approximately 0.7 mg/d) or fed a 10% tomato powder supplemented diet (AIN 93G) for 4 d. Sham-operated rats provided with either phytofluene, lycopene, or tomato powder had approximately 40-50% lower serum testosterone concentrations than the sham-operated, control-fed group. Tissue and serum phytofluene and lycopene concentrations were greater in castrated rats than in sham-operated rats, which may have been due in part to a decrease of hepatic CYP 3A1 mRNA expression and benzyloxyresorufin-O-dealkylase activity. Some changes in prostatic and testicular steroidogenic enzyme mRNA expression were found; in particular, prostate 17 beta-hydroxysteroid dehydrogenase 4 mRNA expression in castrated rats fed lycopene or tomato powder was 1.7-fold that of the sham-operated, control-fed group. Modest changes in mRNA expression of steroidogenic enzymes with short-term carotenoid intake may alter the flux of androgen synthesis to less potent compounds. Overall, results illustrate that short-term intake of tomato carotenoids significantly alters androgen status, which may partially be a mechanism by which tomato intake reduces prostate cancer risk.

Fruits and vegetables contain a variety of phytochemicals, including flavonoids, which have antioxidant and anticancer properties. The purpose of this study was to evaluate the antiproliferative effects and synergistic interactions of a variety of flavonoids in Hepa-1c1c7, a mouse liver cancer cell line, and LNCaP, a human prostate cancer cell line. Aglycone flavonoids, such as quercetin, kaempferol, and naringenin (at 12.5 to 50 μM), inhibited cancer cell proliferation in both cell lines in a dose dependent manner without cytotoxicity. In contrast, glycone flavonoids (rutin, quercetrin, and naringin) did not inhibit cell growth. Significant synergistic antiproliferative effects were demonstrated in both cancer cell lines when flavonoids were provided in combination treatments. These results suggest that combinations of flavonoids, which are naturally present in whole fruits and vegetables, are more effective in cancer cell growth inhibition than the individual flavonoids.

Tomatoes are the fourth most commonly consumed fresh vegetable and the most frequently consumed canned vegetable in the American diet. There is emerging epidemiology data supporting the connection between increased tomato consumption and reduced risk for both cardiovascular disease and prostate cancer. Here we will summarize the nutrient and the phytochemical content of tomatoes and tomato products, and how these bioactive components might act together to modulate disease development. Recent animal studies have investigated tomatoes, lycopene, and prostate cancer using the N-methyl-N-nitrosourea and Dunning rat models. These animal studies also suggest that diets containing tomatoes may decrease the risk or the progression of prostate cancer. Due to the frequency and the extent of tomato consumption, the supporting epidemiological and animal data, which connect increased intakes with decreased cancer and cardiovascular disease risk, tomato's role in the American diet is of undeniable importance as part of a healthy diet.

Mounting evidence over the past decade suggests that the consumption of fresh and processed tomato products is associated with reduced risk of prostate cancer. The emerging hypothesis is that lycopene, the primary red carotenoid in tomatoes, may be the principle phytochemical responsible for this reduction in risk. A number of potential mechanisms by which lycopene may act have emerged, including serving as an important in vivo antioxidant, enhancing cell-to-cell communication via increasing gap junctions between cells, and modulating cell-cycle progression. Although the effect of lycopene is biologically relevant, the tomato is also an excellent source of nutrients, including folate, vitamin C, and various other carotenoids and phytochemicals, such as polyphenols, which also may be associated with lower cancer risk. Tomatoes also contain significant quantities of potassium, as well as some vitamin A and vitamin E. Our laboratory has been interested in identifying specific components or combination of components in tomatoes that are responsible for reducing prostate cancer risk. We carried out cell culture trials to evaluate the effects of tomato carotenoids and tomato polyphenols on growth of prostate cancer cells. We also evaluated the ability of freeze-dried whole-tomato powder or lycopene alone to reduce growth of prostate tumors in rats. This paper reviews the epidemiological evidence, evaluating the relationship between prostate cancer risk and tomato consumption, and presents experimental data from this and other laboratories that support the hypothesis that whole tomato and its phytochemical components reduce the risk of prostate cancer.

Isotopically labeled tomato carotenoids, phytoene, phytofluene, and lycopene, are needed for mammalian bioavailability and metabolism research but are currently commercially unavailable. The goals of this work were to establish and screen multiple in vitro tomato cell lines for carotenoid production, test the best producers with or without the bleaching herbicides, norflurazon and 2-(4-chlorophenyl-thio)-triethylamine (CPTA), and to use the greatest carotenoid accumulator for in vitro 13C-labeling. Different Solanum lycopersicum allelic variants for high lycopene and varying herbicide treatments were compared for carotenoid accumulation in callus and suspension culture, and cell suspension cultures of the hp-1 line were chosen for isotopic labeling. When grown with [U]-13C-glucose and treated with CPTA, hp-1 suspensions yielded highly enriched 13C-lycopene with 45% of lycopene in the M+40 form and 88% in the M+35 to M+40 isotopomer range. To the authors’ knowledge this is the first report of highly enriched 13C-carotenoid production from in vitro plant cell culture.

Tomato product consumption is inversely related to prostate cancer incidence, and lycopene (LYC) has been implicated in reduced prostate cancer risk. The contribution of other tomato carotenoids, phytoene (PE) and phytofluene (PF), towards prostate cancer risk has not been adequately studied. The relative uptake and tissue distribution of tomato carotenoids are not known. We hypothesize that PE and PF are bioavailable from a tomato powder diet or from a purified source and accumulate in androgen-sensitive tissues. In this study, 4 wk old male Fisher 344 rats were pre-fed an AIN-93G powder diet composed of 10% tomato powder containing PE, PF, and LYC (0.015, 0.012, and 0.011 g/kg diet, respectively). After 30 d tomato powder feeding, hepatic PF concentrations (168 ± 20 nmol/g) were higher than PE or LYC (104 ± 13 and 104 ± 13 nmol/g, respectively). In contrast, LYC, followed by PF, had the highest accumulation of the measured carotenoids in the prostate lobes and seminal vesicles. When tomato powder-fed rats received a single oral dose of either ∼2.7 mg PE or PF, an increase in the dosed carotenoid concentration was observed in all measured tissues, except the adrenal. Percent increases of PF were greater than that of PE in liver, serum, and adipose (37, 287 and 49% versus 16, 179 and 23%, respectively). Results indicate that the relative tomato carotenoid biodistribution differs in liver and androgen-sensitive tissues, suggesting that minor changes in the number of sequential double bonds in carotenoid structures alter absorption and/or metabolism of tomato carotenoids.

This work describes the development and utilization of a plant cell culture production approach to biosynthesize and radiolabel phytoene and phytofluene for prostate cancer cell culture studies. The herbicide norflurazon was added to established cell suspension cultures of tomato (Lycopersicon esculentum cv. VFNT cherry), to induce the biosynthesis and accumulation of the lycopene precursors, phytoene and phytofluene, in their natural isomeric forms (15-cis-phytoene and two cis-phytofluene isomers). Norflurazon concentrations, solvent carrier type and concentration, and duration of culture exposure to norflurazon were screened to optimize phytoene and phytofluene synthesis. Maximum yields of both phytoene and phytofluene were achieved after 7 days of treatment with 0.03 mg norflurazon/40 mL fresh medium, provided in 0.07% solvent carrier. Introduction of 14C-sucrose to the tomato cell culture medium enabled the production of 14C-labeled phytoene for subsequent prostate tumor cell uptake studies. In DU 145 prostate tumor cells, it was determined that 15-cis-phytoene and an oxidized product of phytoene were taken up and partially metabolized by the cells. The ability to biosynthesize, radiolabel, and isolate these carotenoids from tomato cell cultures is a novel, valuable methodology for further in vitro and in vivo investigations into the roles of phytoene and phytofluene in cancer chemoprevention.

Key Points Prostate cancer is the second leading cause of cancer death of men in the United States. Americans consume large quantities of tomatoes and tomato products, which contain various nutrients and phytochemicals, including lycopene. Epidemiological evidence strongly indicates a relationship between the increased consumption of tomatoes, tomato products, and lycopene and a reduced risk of prostate cancer. In vitro studies demonstrate that lycopene and other carotenoids decrease cancer cell proliferation in various cancer lines, including prostate cancer cells. In vivo animal studies indicate that consumption of a tomato powder diet delays chemically induced prostate cancer compared to the control diet. Lycopene is found in human tissues and serum and is the major carotenoid found in the human prostate. Plausible mechanisms of action for lycopene include acting as a singlet oxygen quencher, upregulating cellular communication, and modulation of xenobiotic metabolism. Because tomatoes contain a variety of phytochemicals in addition to lycopene, potential interactions and synergies may exist between these compounds to contribute to a reduction in prostate cancer.