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PubMed2006

Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1.

The carotenoid lycopene has been associated with decreased risks of several types of cancer, such as hepatoma. Although lycopene has been shown to inhibit metastasis, its mechanism of action is poorly understood. Here, we used SK-Hep-1 cells (from a human hepatoma) to test whether lycopene exerts its anti-invasion activity via down-regulation of the expression of matrix metalloproteinase (MMP)-9, an important enzyme in the degradation of basement membrane in cancer invasion. The activity and expressions of MMP-9 protein and mRNA were detected by gelatin zymography, Western blotting and RT-PCR, respectively. The binding abilities of nuclear factor-kappa B (NF-kappaB), activator protein-1 and stimulatory protein-1 (Sp1) to the binding sites in the MMP-9 promoter were measured by the electrophoretic mobility shift assay. We showed that lycopene (1-10 microM) significantly inhibited SK-Hep-1 invasion (P<.05) and that this effect correlated with the inhibition of MMP-9 at the levels of enzyme activity (r(2)=.94, P<.001), protein expression (r(2)=.80, P=.007) and mRNA expression (r(2)=.94, P<.001). Lycopene also significantly inhibited the binding abilities of NF-kappaB and Sp1 and decreased, to some extent, the expression of insulin-like growth factor-1 receptor (IGF-1R) and the intracellular level of reactive oxygen species (P<.05). The antioxidant effect of lycopene appeared to play a minor role in its inhibition of MMP-9 and invasion activity of SK-Hep-1 cells because coincubation of cells with lycopene plus hydrogen peroxide abolished the antioxidant effect but did not significantly affect the anti-invasion ability of lycopene. Thus, lycopene decreases the invasive ability of SK-Hep-1 cells by inhibiting MMP-9 expression and suppressing the binding activity of NF-kappaB and Sp1. These effects of lycopene may be related to the down-regulation of IGF-1R, while the antioxidant activity of lycopene appears to play a minor role.

Anticarcinogenic Agents↗

PubMed2005

Inhibitory effects of lycopene on in vitro platelet activation and in vivo prevention of thrombus formation.

Lycopene is a natural carotenoid antioxidant that is present in tomatoes and tomato products. The pharmacologic function of lycopene in platelets is not yet understood. Therefore, in this study we sought to systematically examine the effects of lycopene in the prevention of platelet aggregation and thrombus formation. We found that lycopene concentration-dependently (2-12 micromol/L) inhibited platelet aggregation in human platelets stimulated by agonists. Lycopene (6 and 12 micromol/L) inhibited phosphoinositide breakdown in platelets labeled with tritiated inositol, intracellular Ca+2 mobilization in Fura-2 AM-loaded platelets, and thromboxane B2 formation stimulated by collagen. In addition, lycopene (6 and 12 micromol/L) significantly increased the formations of cyclic GMP and nitrate but not cyclic AMP in human platelets. Rapid phosphorylation of a protein of 47,000 Da (P47), a marker of protein kinase C activation, was triggered by PDBu (60 nmol/L). This phosphorylation was markedly inhibited by lycopene (12 micromol/L) in phosphorus-32-labeled platelets. In an in vivo study, thrombus formation was induced by irradiation of mesenteric venules in mice pretreated with fluorescein sodium. Lycopene (5, 10, and 20 mg/kg) significantly prolonged the latency period for the induction of platelet-plug formation in mesenteric venules. These results indicate that the antiplatelet activity of lycopene may involve the following pathways: (1) Lycopene may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown and thromboxane B2 formation, thereby leading to inhibition of intracellular Ca+2 mobilization. (2) Lycopene also activated the formations of cyclic GMP/nitrate in human platelets, resulting in the inhibition of platelet aggregation. The results may imply that tomato-based foods are especially beneficial in the prevention of platelet aggregation and thrombosis.

Animals↗

PubMed2002

Effect of lycopene on prostate LNCaP cancer cells in culture.

Epidemiological studies have shown an inverse relationship between serum lycopene levels and the risk of prostate cancer. The objective of this study was to measure the effect of lycopene on the proliferation of LNCaP human prostate cancer cells in culture. A new, water-dispersible lycopene in an appropriate vehicle was used. The stock solution was diluted in the medium to obtain lycopene concentrations of 10(-6), 10(-5), and 10(-4) M; their corresponding vehicles were similarly diluted to be used as controls. Cells were grown for 48 hours in RPMI-1640 medium supplemented with 10% fetal bovine serum and antibiotics. Lycopene was then added at different concentrations, and the cells were allowed to grow for 24, 48, 72, and 96 hours. Lycopene at concentrations of 10(-6) and 10(-5) M significantly reduced the growth of LNCaP cells after 48, 72, and 96 hours of incubation, by 24.4% to 42.8% (P <.05). The inhibitory effect of lycopene was significantly higher than that of the corresponding vehicle controls. In a follow-up experiment, a lower range of lycopene concentrations (10(-9) to 10(-7) M) was used to determine whether there was a dose-response effect. Lycopene significantly decreased the growth of cells in a dose-dependent manner when cells were incubated for 24, 48, 72, or 96 hours (F = 3.150, 11.27, 54.51, and 297.5, respectively; P <.05). The growth inhibitory effect of lycopene on human prostate cancer cells observed in this study suggests a possibly important role for lycopene as an antioxidant in human prostate cancer; however, investigations of other mechanisms are warranted.

Anticarcinogenic Agents↗

PubMed1999

Carotenoids in human buccal mucosa cells after 4 wk of supplementation with tomato juice or lycopene supplements.

BACKGROUND: Lycopene has been identified as a phytochemical with potentially protective health benefits. OBJECTIVE: Our objective was to monitor lycopene changes in buccal mucosa cells (BMCs) in response to 3 vehicles for oral delivery of lycopene. DESIGN: Fifteen healthy subjects ingested lycopene-rich tomato juice, tomato oleoresin, lycopene beadlets (each containing 70-75 mg lycopene) and a placebo for 4 wk each in a randomized crossover design while consuming self-selected diets. A 6-wk washout period separated the treatment periods. BMCs were collected at baseline and after 4 wk of supplementation. RESULTS: Lycopene in BMCs increased significantly ( approximately 2-fold) after 4 wk of ingestion of oleoresin and of beadlets to 4.95 (P < 0.001) and 3.75 microg/g protein (P = 0.053), respectively, but was not significantly affected by tomato juice treatment. The placebo treatment produced a significant decrease in BMC lycopene concentrations (P = 0.018). We observed significant treatment differences between oleoresin and tomato juice, oleoresin and placebo, and beadlets and placebo. BMC concentrations of phytofluene and beta-carotene, which were present in small amounts in the lycopene-containing treatments, increased significantly with ingestion of these products. Strong correlations were found between plasma and BMC concentrations of lutein, beta-cryptoxanthin, alpha-carotene, and beta-carotene. In contrast, correlations between lycopene concentrations in plasma and in BMCs were weak and not significant for any treatment. CONCLUSIONS: The cellular content of lycopene and other tomato-related carotenoids with proposed beneficial health effects can be increased through prolonged supplementation.

Adult↗

PubMed2003

Serum lycopene concentrations and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND: Interest in lycopene is growing rapidly following the recent publication of epidemiologic studies in which high circulating lycopene concentrations were associated with reductions in cardiovascular disease. Lycopene is one of the major carotenoids in the Western diet and is probably one of the protective factors in a vegetable-rich diet. OBJECTIVE: We studied the hypothesis that the intima-media thickness of the common carotid artery (CCA-IMT) would be greater in men with low serum lycopene concentrations. DESIGN: We investigated the relation between serum lycopene concentration and CCA-IMT in 1028 middle-aged men (aged 46-64 y) in eastern Finland who were participants in the Kuopio Ischaemic Heart Disease Risk Factor study and who were examined in 1991-1993. The subjects were classified into quarters according to serum lycopene concentration. RESULTS: In a covariance analysis with adjustment for covariates, the men in the lowest quarter of serum lycopene concentration had a significantly higher mean CCA-IMT and maximal CCA-IMT (P = 0.005 and P = 0.001 for the difference, respectively) than did the other men. The mean and maximal CCA-IMT increased linearly across the quarters of serum lycopene concentration. CONCLUSIONS: A low serum lycopene concentration is associated with a higher CCA-IMT in middle-aged men from eastern Finland. This finding suggests that the serum lycopene concentration may play a role in the early stages of atherosclerosis. Increased thickness of the intima-media has been shown to predict coronary events; thus, lycopene intakes and serum concentrations may have clinical and public health relevance.

Arteriosclerosis↗

PubMed2001

Testosterone and food restriction modulate hepatic lycopene isomer concentrations in male F344 rats.

We previously demonstrated that the castration of male rats profoundly increases hepatic lycopene compared with intact controls. Here we further characterized the role of testosterone in modulating hepatic lycopene accumulation and isomer patterns in male rats. Furthermore, because castration significantly decreases ad libitum food consumption, we investigated the influence of food restriction on lycopene metabolism. Forty male F344 rats 8 wk of age were randomly assigned to one of four treatments (n = 10/group): 1) intact, free access to food, 2) castration, free access to food, 3) castration plus testosterone implants, free access to food and 4) intact, 20% food restricted. All rats were fed an AIN-based diet with 0.25 g lycopene (as 10% water-soluble beadlets)/kg diet for 3 wk. Serum testosterone was 5.31 +/- 1.46 nmol/L in intact controls allowed free access to food, reduced in castrated animals (0.52 +/- 0.10, P < 0.0001 versus controls) and intact, food-restricted rats (1.53 +/- 0.49 nmol/L, P < 0.0001 versus controls) and greater (17.23 +/- 3.09 nmol/L) in castrated rats administered testosterone (P < 0.0001 versus controls). Castrated rats accumulated approximately twice as much liver lycopene (74.5 +/- 8.5 nmol/g; P < 0.01 versus controls) as intact rats allowed free access to food (39.5 +/- 5.0) despite 13% lower dietary lycopene intake (P < 0.001; 3.38 +/- 0.07 versus 3.95 +/- 0.06 mg lycopene/d). Testosterone replacement in castrated rats returned liver lycopene concentrations (32.5 +/- 5.5 nmol lycopene/g with 3.76 +/- 0.05 mg dietary lycopene/d) to those observed in intact rats. Food restriction resulted in a 20% decrease in lycopene intake but significantly increased liver lycopene by 68% (66.3 +/- 7.9 nmol lycopene/g with 3.38 +/- 0.00 mg lycopene/d) compared with controls and castrated rats administered testosterone. These results suggest that androgen depletion and 20% food restriction increase hepatic lycopene accumulation. We hypothesize an endocrine and dietary interaction, where higher androgen concentrations and greater energy intake may stimulate lycopene metabolism and degradation.

Adrenal Glands↗

PubMed2003

Consumption of watermelon juice increases plasma concentrations of lycopene and beta-carotene in humans.

Watermelon is a rich natural source of lycopene, a carotenoid of great interest because of its antioxidant capacity and potential health benefits. Assessment of bioavailability of lycopene from foods has been limited to tomato products, in which heat processing promotes lycopene bioavailability. We examined the bioavailability of lycopene from fresh-frozen watermelon juice in a 19-wk crossover study. Healthy, nonsmoking adults (36-69 y) completed three 3-wk treatment periods, each with a controlled, weight-maintenance diet. Treatment periods were preceded by "washout" periods of 2-4 wk during which lycopene-rich foods were restricted. All 23 subjects consumed the W-20 (20.1 mg/d lycopene, 2.5 mg/d beta-carotene from watermelon juice) and C-0 treatments (controlled diet, no juice). As a third treatment, subjects consumed either the W-40 (40.2 mg/d lycopene, 5.0 mg/d beta-carotene from watermelon juice, n = 12) or T-20 treatment (18.4 mg/d lycopene, 0.6 mg/d beta-carotene from tomato juice, n = 10). After 3 wk of treatment, plasma lycopene concentrations for the W-20, W-40, T-20 and C-0 treatments were (least squares means +/- SEM) 1078 +/- 106, 1183 +/- 139, 960 +/- 117 and 272 +/- 27 nmol/L, respectively. Plasma concentrations of beta-carotene were significantly greater after W-20 (574 +/- 49 nmol/L) and W-40 (694 +/- 73 nmol/L) treatments than after the C-0 treatment (313 +/- 27 nmol/L). Plasma lycopene concentrations did not differ at wk 3 after W-20, W-40 and T-20 treatments, indicating that lycopene was bioavailable from both fresh-frozen watermelon juice and canned tomato juice, and that a dose-response effect was not apparent in plasma when the watermelon dose was doubled.

Adult↗

PubMed2003

Pharmacokinetics and tissue distribution of orally administered lycopene in male dogs.

Consumption of lycopene, the predominant carotenoid in tomatoes and tomato products, is associated with reduced prostate cancer risk. The purpose of this study was to measure the pharmacokinetics and tissue distribution of lycopene after oral administration to male dogs. After single doses of 10, 30 and 50 mg/kg body weight (BW) lycopene to 2 dogs/dose, the mean half-life was 36 h and the plasma systemic exposure levels (AUC(0-)( infinity ), area under the curve) after the 30 and 50 mg/kg BW doses were similar. In a repeat dose study, 30 mg/(kg BW. d) administered orally to six dogs for 28 d resulted in steady-state plasma concentrations between 785 and 997 nmol/L lycopene. Apparent clearance, volume of distribution and apparent elimination half-life were 2.29 L/(h. kg), 96 L/kg and 30.5 h, respectively. Dogs were killed 1 or 5 d after the last dose and 23 tissues were collected for lycopene analysis. Lycopene concentrations were highest in liver, adrenals, spleen, lymph nodes and intestinal tissues. Liver lycopene concentrations were 66 and 91 nmol/g 1 and 5 d after cessation of treatment, respectively. Prostate lycopene concentrations were < 0.2 nmol/g both 1 and 5 d after dosing ceased (<0.4% of liver concentrations). Although 70% trans-lycopene was used in the dosing material, most of the lycopene identified in plasma and tissues was cis-lycopene.

Administration, Oral↗

PubMed2004

Enteral administration of soybean phosphatidylcholine enhances the lymphatic absorption of lycopene, but reduces that of alpha-tocopherol in rats.

Dietary phosphatidylcholine (PC) increases the lymphatic absorption of triglyceride (TG). This result suggests that dietary PC might also enhance the absorption of other fat-soluble nutrients. We examined the effects of PC on lycopene and alpha-tocopherol absorption in male rats fitted with a thoracic lymph cannula. The lymphatic output was collected after administration of 1 mL of emulsified test oils containing lycopene and/or alpha-tocopherol in 3 separate experiments. The sodium taurocholate-emulsified test oils contained soybean oil (SO; 113 micromol triglyceride), SO containing soybean PC (SPC; 82.5 micromol SO plus 30.5 micromol purified soybean PC) or SO containing egg PC (EPC; 82.5 micromol SO plus 30.5 micromol purified egg PC) with both lycopene and alpha-tocopherol (Expt. 1) or SO, SPC, or EPC with lycopene (Expt. 2) or alpha-tocopherol alone (Expt. 3). In rats administered SPC or EPC, the lymphatic outputs of TG and lycopene were higher, and that of alpha-tocopherol was lower compared with rats administered SO (Expt. 1). The absorption rate for lycopene increased from 0.59% (SO group) to 2.16 and 1.28% in the SPC and EPC groups (P < 0.05), respectively, whereas the corresponding rates for tocopherol were 21.5% for the SO, 14.8% for the SPC, and 12.9% for the EPC groups. The increase in lycopene, but not in triglyceride absorption, was higher in the SPC than in the EPC groups. The promotive effects of SPC and EPC were decreased when lycopene alone was added to the test lipids (Expt. 2), and the inhibitory effects of PC were reduced when alpha-tocopherol alone was added to the test lipids (Expt. 3). Dietary PC increased the lymphatic output of lycopene and TG and decreased that of alpha-tocopherol, suggesting that differences exist between lycopene and alpha-tocopherol in the absorptive mechanisms. The present results also show that the promotive effects of PC on lycopene absorption are influenced by the type of fatty acids in PC.

Animals↗

PubMed2005

Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice.

Lycopene is a promising chemopreventive agent for human prostate cancer. To test the hypothesis that the effect of lycopene on prostate cancer is stage specific in the process of carcinogenesis, inhibitory effects of natural lycopene on the proliferation of 3 different human prostate carcinoma cell lines were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Lycopene more potently inhibited the growth of the androgen-independent DU145 and PC-3 cells than androgen-dependent LNCaP cells. The 50% inhibitory concentration of lycopene for these cell lines was 26.6 micromol/L for DU145, 40.3 micromol/L for PC-3, and 168.5 micromol/L for LNCaP. We also studied the inhibitory effect of lycopene on the growth rate of DU145 tumor xenografts in BALB/c male nude mice. The tumor growth rate was inhibited by 55.6 and 75.8% in mice treated with 100 and 300 mg/kg lycopene, respectively, compared with controls. In addition, no tumors formed in 1 mo in mice treated with DU145 cells that had been pretreated with 20 micromol/L lycopene; however, they did form when DU145 cells were not pretreated. Flow cytometry revealed that lycopene caused DU145 cells to accumulate in the G(0)/G(1) phase and to undergo apoptosis in a dose-dependent manner. The rate of apoptosis was up to 42.4% lower in DU145 cells treated with 32 micromol/L lycopene compared with the untreated control cells. These results suggest that lycopene may specifically inhibit the growth of androgen-independent prostate cancers.

Animals↗

PubMed2005

Lycopene inhibits cell migration and invasion and upregulates Nm23-H1 in a highly invasive hepatocarcinoma, SK-Hep-1 cells.

The carotenoid lycopene has been associated with decreased risks of several types of cancer, such as prostate cancer and hepatoma. Tumor metastasis is the most important cause of cancer death. Although lycopene was shown to inhibit metastasis, the mechanism underlying this action is not well understood. Here, we tested the possibility that lycopene may inhibit cancer cell metastasis by upregulating the expression of nm23-H1, a metastasis suppressor gene, in SK-Hep-1 cells, a highly invasive hepatoma cell line, and we determined migration and invasion activities and the expression of nm23-H1 protein and mRNA. We showed that lycopene inhibited SK-Hep-1 migration and invasion in a bell-shaped manner, with the highest effect at 5 micromol/L (91 and 63% inhibition for migration and invasion, respectively; P < 0.05). At the same test level (10 micromol/L), lycopene was much more effective than beta-carotene in reducing cell invasion (by approximately 870%). In contrast to the effects on migration and invasion, lycopene enhanced nm23-H1 expression at both the protein and mRNA levels; the effects were also bell shaped, and at 5 micromol/L, lycopene enhanced nm23-H1 protein and mRNA expressions by 220 +/- 33 and 153 +/- 22% (P < 0.01), respectively. These bell-shaped effects of lycopene may be related to autoxidation of lycopene at elevated concentrations (> or =10 micromol/L). Significant correlations existed between nm23-H1 protein expression and migration (r2= 0.78, P < 0.001) and between nm23-H1 protein expression and invasion (r2= 0.84, P < 0.001) in lycopene-treated SK-Hep-1 cells. We conclude that lycopene has significant antimigration and anti-invasion activity, and that this effect is associated with its induction of nm23-H1 expression.

Anticarcinogenic Agents↗

PubMed2006

Lycopene supplementation prevents smoke-induced changes in p53, p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets.

Cigarette smoking increases the risk for gastric cancer. Higher intakes or blood levels of lycopene are associated with a decreased risk of gastric cancer. However, the biological mechanisms by which lycopene may protect against gastric carcinogenesis are poorly understood. We evaluated the effects of lycopene supplementation on smoke-induced changes in protein levels of p53, p53 target genes (p21(Waf1/Cip1) and Bax-1), cell proliferation, and apoptosis in the gastric mucosa of ferrets. Ferrets were assigned to cigarette smoke exposure or to no exposure and to no, low-dose, or high-dose lycopene supplementation (2 x 3 factorial design) for 9 wk. Lycopene concentrations were significantly elevated in a dose-dependent manner in the gastric mucosa of ferrets supplemented with lycopene alone, but were markedly reduced in ferrets supplemented with lycopene and exposed to smoke. Although ferrets were given lycopene containing 95% all-trans isomers, cis isomers were the predominant forms in the gastric mucosa. Total p53 and phosphorylated p53 levels were greater in ferrets exposed to smoke alone than in all other groups. Levels were approximately 300 and 500% of the controls, respectively. However, smoke-elevated total p53 and phosphorylated p53 were markedly attenuated by both doses of lycopene. p21(Waf1/Cip1), Bax-1, and cleaved caspase 3 were substantially decreased, whereas cyclin D1 and proliferating cellular nuclear antigen (PCNA) were increased in ferrets exposed to smoke alone. Lycopene prevented smoke-induced changes in p21(Waf1/Cip1), Bax-1, cleaved caspase 3, cyclin D1, and PCNA in a dose-dependent fashion. These data indicate that lycopene may prevent smoke exposure-induced changes in p53, p53 phosphorylation, p53 target genes, cell proliferation, and apoptosis in the gastric mucosa of ferrets.

Animals↗

PubMed2000

Correlates of serum lycopene in older women.

Experimental and epidemiological evidence suggests that lycopene, a predominant carotenoid found in human serum, may reduce the risk of certain cancers. We examined the association of dietary, physiological, and other factors with serum lycopene concentrations in a subsample of 946 postmenopausal women participating in the Women's Health Initiative. Pearson partial correlation coefficients and linear regression coefficients were calculated after adjustment for age, ethnicity, and serum low-density-lipoprotein (LDL) cholesterol. Serum lycopene was correlated with serum LDL cholesterol (r = 0.23) and dietary lycopene (r = 0.17, both p < 0.001). Individual food items found to be correlated with serum lycopene after adjustment included fresh tomatoes or tomato juice (r = 0.11), cooked tomatoes, tomato sauce, or salsa (r = 0.17), and spaghetti with meat sauce (r = 0.19, all p < 0.01). Age and body mass index were negatively associated with serum lycopene levels (both p < 0.001). Serum lycopene levels were highest in the summer and highest for those living in the northeastern United States. If we postulate that high serum lycopene levels reduce cancer risk, it becomes apparent that we have limited ability to detect this association from studies of lycopene intake. An understanding of factors associated with serum lycopene levels can be useful for the interpretation of studies of dietary lycopene and disease risk.

Aged↗

PubMed2004

Lycopene supplementation prevents the development of spontaneous smooth muscle tumors of the oviduct in Japanese quail.

Leiomyomas (fibroids) are benign tumors of the uterus affecting millions of women. Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica), which makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Because dietary intake of lycopene has been associated with a reduced risk of a variety of human cancers, we investigated the effects of lycopene supplementation on the development of leiomyomas in the oviduct of Japanese quail. We also measured serum levels of oxidative stress markers [malondialdehyde (MDA) and homocysteine], lycopene, vitamins C, E, and A, and tissue biomarkers Bcl-2 and Bax expression. One hundred twenty quails (6 mo old) were assigned to 3 treatment groups consisting of 4 replicates of 10 birds in each group. Birds were fed either a basal diet (group C) or the basal diet supplemented with 100 mg (group L1) or 200 mg (group L2) of lycopene per kilogram of diet. The animals were sacrificed after 285 days and the tumors were identified. Lycopene supplementation decreased the number of leiomyomas compared with control subjects (P=0.056). The tumors in lycopene-fed birds were smaller than those found in control birds (P=0.01). There were no significant differences in the expression of tissue Bcl-2 and Bax among the study groups. Serum vitamins C, E, and A increased (P=0.01), whereas MDA and homocysteine concentrations decreased (P=0.01) with lycopene supplementation. No measurable lycopene could be detected in the serum of control birds, whereas a dose-dependent increase was observed in the serum of lycopene-supplemented birds. The results indicate that dietary supplementation with lycopene reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of lycopene supplementation in the prevention and treatment of uterine leiomyoma in humans.

Animals↗

PubMed2006

Plasma profiles of lycopene after single oral and intravenous administrations in dogs.

The objectives of this study were to identify the factors limiting the absorption of purified lycopene after oral administration, and to comparatively assess plasma data sets after single oral and intravenous administrations in dogs to define the conditions for performing an absolute bioavailability study. Solubility of purified lycopene (all-trans, 93.5%) was determined in media simulating the conditions in the fasted and in the fed upper gastrointestinal lumen. After evaluating the plasma levels achieved following single administrations of purified lycopene powder to fasted and fed dogs at escalating doses (75-750 mg), a crossover study was performed in four fed female mongrel dogs at two phases. In phase I, one soft gelatine capsule (10 mg lycopene) with 500 mL milk was administered orally. In phase II, 500 mL milk was administered orally and 250 mL 5% dextrose containing 5 mg lycopene in the form of a binary system with hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was administered intravenously over 3.5 h. In-vitro and preliminary canine studies confirmed that, after oral administration of lycopene in solid form, arrival of lycopene into the systemic circulation was limited by lymphatic transport and, in addition, if the administered dose was higher than approximately 2 mg, by intralumenal solubility. During the first 50 h after single administrations to fed dogs, lycopene plasma levels were lower after intravenous than after oral administration. This could have been related to capacity limited elimination of lycopene and/or route-dependent disposition kinetics. Estimation of the amount of lycopene reaching the systemic circulation after oral and after intravenous administration requires separate estimations of total body clearance of lycopene.

Administration, Oral↗

PubMed2005

[The measurement and analysis of visible-absorption spectrum and fluorescence spectrum of lycopene].

Using ICCD spectral detection system, the absorbency of lycopene-carbon bisulfide solution with different concentration was measured, and the result shows that in a specified range the absorption rule of lycopene solution agrees with Lambert-Beer Law. Absorption spectral wavelength shifts were measured respectively when lycopene was dissolved in acetone, normal hexane, petroleum ether, benzene, ethyl acetate, and carbon bisulfide, and comparing to acetone, different red-shift appeared when lycopene was dissolved in benzene, ethyl acetate, and carbon bisulfide when water was added in lycopene-acetone solution, t he absorbency of lycopene dropped, the fine structure of absorption spectrum became indistinct, and a new absorption peak appeared in UV. The reason for these phenomena is that the solvent molecule had different effect on lycopene molecule when lycopene was dissolved in different solvent. Using fluorecence spectrophotometer, fluorescence spectra of lycopene in different concentrations were collected, and the results show that the fluorescence spectra of lycopene were mainly in 500-680 nm. When concentration was lower than 50 microg x mL(-1), the fluorescence intensity linearly increased with increasing concentration, and when concentration was higher than 60 microg x mL(-1), the fluorescence intensity dropped because of the interaction between lycopene molecules.

Carotenoids↗

PubMed2005

Identification of genes affecting lycopene accumulation in Escherichia coli using a shot-gun method.

Genes enhancing lycopene production in Escherichia coli were identified through colorimetric screening of shot-gun library clones constructed with E. coli chromosomal DNA. These E. coli cells had been engineered to produce lycopene, a red-colored carotenoid, which enabled screening for genes that enhance lycopene production. Six clones with enhanced lycopene production were isolated. Among 13 genes in these clones, dxs, appY, crl, and rpoS were found to be involved in enhanced lycopene production. While dxs and rpoS have been already reported to enhance lycopene production, appY and crl have not. DXP (1-deoxy-D-xylulose-5-phosphate) synthase is encoded by dxs and participates in the rate-limiting step in the synthesis of isopentenyl pyrophosphate (IPP), a building block of lycopene. Sigma S factor, encoded by rpoS, regulates transcription of genes induced at the stationary phase. The appY and crl genes encode transcriptional regulators related to anaerobic energy metabolism and the formation of curli surface fibers, respectively. E. coli harboring appY plasmids produced 2.8 mg lycopene/g dry cell weight (DCW), the same amount obtained with dxs despite the fact that appY is not directly involved in the lycopene synthesis pathway. The co-expression of appY, crl, and rpoS with dxs synergistically enhanced lycopene production. The co-expression of appY with dxs produced eight times the amount of lycopene (4.7 mg/g DCW) that was produced without expression of both genes (0.6 mg/g DCW).

Biolistics↗

PubMed2006

Engineering the lycopene synthetic pathway in E. coli by comparison of the carotenoid genes of Pantoea agglomerans and Pantoea ananatis.

The lycopene synthetic pathway was engineered in Escherichia coli using the carotenoid genes (crtE, crtB, and crtI) of Pantoea agglomerans and Pantoea ananatis. E. coli harboring the P. agglomerans crt genes produced 27 mg/l of lycopene in 2YT medium without isopropyl-beta-D: -thiogalactopyranoside (IPTG) induction, which was twofold higher than that produced by E. coli harboring the P. ananatis crt genes (12 mg/l lycopene) with 0.1 mM IPTG induction. The crt genes of P. agglomerans proved better for lycopene production in E. coli than those of P. ananatis. The crt genes of the two bacteria were also compared in E. coli harboring the mevalonate bottom pathway, which was capable of providing sufficient carotenoid building blocks, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), with exogenous mevalonate supplementation. Lycopene production significantly increased using the mevalonate bottom pathway and 60 mg/l of lycopene was obtained with the P. agglomerans crt genes, which was higher than that obtained with the P. ananatis crt genes (35 mg/l lycopene). When crtE among the P. ananatis crt genes was replaced with P. agglomerans crtE or Archaeoglobus fulgidus gps, both lycopene production and cell growth were similar to that obtained with P. agglomerans crt genes. The crtE gene was responsible for the observed difference in lycopene production and cell growth between E. coli harboring the crt genes of P. agglomerans and P. ananatis. As there was no significant difference in lycopene production between E. coli harboring P. agglomerans crtE and A. fulgidus gps, farnesyl diphosphate (FPP) synthesis was not rate-limiting in E. coli.

Bacterial Proteins↗