Selective growth inhibition of human leukemia and human lymphoblastoid cells by resveratrol via cell cycle arrest and apoptosis induction

There is great interest in the potential chemopreventive activity of resveratrol against human cancers. However, there are conflicting results on its growth inhibitory effect on normal cells. This project examined the differential effect of resveratrol at physiologically relevant concentrations on nonmalignant (WIL2-NS) and malignant (HL-60) cell lines and compared the underlying mechanisms via cell cycle modulation, apoptosis induction, and genotoxicity potential. Twenty-four hours of exposure to resveratrol was toxic to WIL2-NS and HL-60 cells in a dose-dependent manner. WIL2-NS cells regrew 5 times more than HL-60 cells by 120 h after the removal of 100 microM resveratrol (p < 0.05). Furthermore, significant alterations in cell cycle kinetics were induced by resveratrol in HL-60 cells, but were to a lesser extent for WIL2-NS cells. The proportion of apoptosis was also 3 times higher in HL-60 cells as compared to WIL2-NS cells for 100 microM resveratrol (p < 0.05). In conclusion, resveratrol preferentially inhibited the growth of HL-60 cells via cell cycle modulation and apoptosis induction and subsequently directed the cells to irreversible cell death, whereas the effect on WIL2-NS cells was largely reversible.     

Cranberry proanthocyanidins induce apoptosis and inhibit acid-induced proliferation of human esophageal adenocarcinoma cells

The occurrence of esophageal adenocarcinoma and its only recognized precursor lesion, Barrett's esophagus, has rapidly increased during the past three decades. The precise reason for the rise remains to be elucidated, but increasing rates have been linked to multiple nutritional factors. Plant-based diets have generally been associated with a reduction of risk for esophageal adenocarcinoma and those of animal origin with risk escalation. Moreover, a number of recent in vitro and limited in vivo investigations have reported that cranberry extracts affect multiple cancer-associated processes in breast, colon, prostate, and other cancer cell lines of epithelial origin. Thus, this study sought to investigate the chemopreventive potential of a cranberry proanthocyanidin rich extract (PAC) in SEG-1 human esophageal adenocarcinoma (EAC) cells. PAC pretreatment significantly inhibited the viability and proliferation of EAC cells in a time- and dose-dependent manner. Moreover, PAC (50 microg/mL) significantly inhibited acid-induced cell proliferation of SEG-1 cells. PAC treatment induced cell cycle arrest at the G1 checkpoint and significantly reduced the percentage of SEG-1 cells in S-phase following 24 and 48 h of exposure. PAC treatment also resulted in significant induction of apoptosis. Thus, PAC modulates cell cycle regulation, aberrant proliferation, and apoptosis, all key biological processes altered during progression to esophageal adenocarcinoma. These findings support that further mechanistic studies are warranted to more fully elucidate the inhibitory potential of PAC against esophageal cancer.     

Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side-by-side comparison

The effects of resveratrol and pterostilbene (two structurally related stilbene compounds) on three human colon cancer cells were systematically compared. Cell viability tests indicated that IC(50) values of pterostilbene were 2-5-fold lower than those of resveratrol in all three cancer cells. Pterostilbene was also more potent in inhibiting colony formation of all three cancer cells. Annexin V/propidium iodide costaining assay and Western blotting analysis showed pterostilbene had a stronger apoptosis-inducing effect, which was evidenced by the higher percentage of annexin V positive cells and higher levels of cleaved caspase-3 and poly(ADP-ribose) polymerase proteins in cancer cells treated with pterostilbene compared with resveratrol. High-performance liquid chromatography analysis demonstrated that intracellular levels of pterostilbene were 2-4-fold higher than those of resveratrol after treatments with individual compounds at the same concentration. Overall, the results demonstrated that pterostilbene had more potent inhibitory effects on colon cancer cells than resveratrol, which may be associated with the superior bioavailability of pterostilbene to resveratrol.     

Effect of black soybean extract on the suppression of the proliferation of human AGS gastric cancer cells via the induction of apoptosis

Black soybean is known to have a health-promoting effect because of its high content of polyphenolic compounds and antioxidant activities. The objective of the present study was to investigate the chemopreventive effects of black soybean extract against human AGS gastric cancer cells and its possible mechanism in inducing apoptosis. Black soybean extract was obtained by extracting black soybean with acidified aqueous acetone, and its phytochemical constituents, as determined by HPLC-DAD methods, were demonstrated to contain various phenolics. The black soybean extract inhibited AGS cell growth in a dose-dependent manner with an IC(50) of 3.69 mg/mL as measured by the MTT assay. This growth inhibition effect was further confirmed by the CFDA-SE assay. Flow cytometry analysis showed that black soybean extract dose-dependently induced apoptosis of AGS cells. Moreover, the involvement of black soybean extract in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, caspase-3, and PARP. The results of the present study indicated that black soybean extract could be used as an apoptosis inducer in AGS cells and a natural chemopreventive agent in the treatment of human gastric cancer.     

Apple polyphenols affect protein kinase C activity and the onset of apoptosis in human colon carcinoma cells

Polyphenol-rich apple extracts have been reported to suppress human colon cancer cell growth in vitro. The protein kinase C (PKC) is among the signaling elements known to play an important role in colon carcinogenesis. In the present study, we investigated whether apple polyphenols affect PKC activity and induce apoptosis in the human colon carcinoma cell line HT29. A polyphenol-rich apple juice extract (AE02) was shown to inhibit cytosolic PKC activity in a cell-free system. In contrast, incubation of HT29 cells for 1 or 3 h with AE02 up to 2 mg/mL did not affect the cytosolic PKC activity. After prolonged incubation (24 h), cytosolic PKC activity was modulated, albeit a u-shaped curve of effectiveness was observed, with an initial inhibitory effect followed by the recurrence and even induction of enzyme activity. Concomitantly, in the cytosol, a significant decrease of the protein levels of PKCalpha, PKCbetaII, and PKCgamma together with a significant increase of a proapoptotic PKCdelta fragment was observed. However, the effects on the protein levels of these PKC isoforms in the cytosol were not associated with translocation between the different cellular compartments but might instead result from the onset of apoptosis. Indeed, the treatment with AE02 was shown to induce apoptosis by the activation of caspase-3, DNA fragmentation, and cleavage of poly(ADP ribose) polymerase. So far, identified and available constituents of the apple extract did not contribute substantially to the observed effects on PKC and apoptosis induction. In summary, apple polyphenols were found to inhibit PKC activity in a cell-free system. However, our results indicate that within intact cells PKC does not represent the primary target of apple polyphenols but appears to be affected in the course of apoptosis induction.     

Evaluation of reduced toxicity of zearalenone by extrusion processing as measured by the MTT cell proliferation assay

The objective of this study was to determine loss of toxicity of zearalenone in extruded cereal-based products by the MTT (tetrazolium salt) cell proliferation assay using a sensitive MCF-7 human breast cancer cell line and to compare the results to chemical (high-performance liquid chromatography, HPLC) and biochemical (enzyme-linked immunosorbent assay, ELISA) methods of analysis. A split-split plot design was used for the extrusion process experiments at temperatures of 150, 175, and 200 degrees C and screw speeds of 70 and 140 rpm. The initial zearalenone concentration in the artificially contaminated corn grits with Fusarium graminearum was found at a mean concentration of 37.88 microg/g as measured by HPLC. The percent reductions of zearalenone in the contaminated corn grits upon extrusion processing were in the ranges of 67-81, 60-72, and 66-78% as measured by HPLC, ELISA, and the MTT cell proliferation assay, respectively. The MTT cell proliferation assay results were more closely correlated with HPLC results (r = 0.96) than ELISA results (r = 0.83). The MTT cell proliferation assay was demonstrated to be a useful method for quantification of zearalenone as well as a potential toxicity screening method for contaminated extruded cereal-based products.     

长期施肥对土壤氮矿化的影响

Two field experiments were conducted in Jiashan and Yuhang towns of Zhejiang Province, China, to study the feasibility of predicting N status of rice using canopy spectral reflectance. The canopy spectral reflectance of rice grown with different levels of N inputs was determined at several important growth stages. Statistical analyses showed that as a result of the different levels of N supply, there were significant differences in the N concentrations of canopy leaves at different growth stages. Since spectral reflectance measurements showed that the N status of rice was related to reflectance in the visible and NIR （near-infrared） ranges, observations for rice in 1 nm bandwidths were then converted to bandwidths in the visible and NIR spectral regions with IKONOS （space imaging） bandwidths and vegetation indices being used to predict the N status of rice. The results indicated that canopy reflectance measurements converted to ratio vegetation index （RVI） and normalized difference vegetation index （NDVI） for simulated IKONOS bands provided a better prediction of rice N status than the reflectance measurements in the simulated IKONOS bands themselves. The precision of the developed regression models using RVI and NDVI proved to be very high with R2 ranging from 0.82 to 0.94, and when validated with experimental data from a different site, the results were satisfactory with R2 ranging from 0.55 to 0.70. Thus, the results showed that theoretically it should be possible to monitor N status using remotely sensed data.     

Identification of urolithin a as a metabolite produced by human colon microflora from ellagic acid and related compounds

Dietary ellagic acid and related polyphenols are metabolized in humans to dibenzopyran-6-one derivatives, and the microbial origin of these metabolites has been suggested. However, this has not been demonstrated so far. Fecal samples donated by six volunteers were incubated under anaerobic conditions, and aliquots were used to evaluate the fecal metabolism of ellagic acid, the ellagitannin punicalagin, and an ellagitannin rich extract from walnuts. The isoflavone daidzein was also incubated with the same fecal samples to follow the production of the microbial metabolites previously reported (dihydrogenistein, O-demethylangolensin, and equol) as a positive control of the system and to evaluate similarities between isoflavone and ellagic acid fecal flora metabolism. After fermentation the metabolite "urolithin A" (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one) was produced from ellagic acid, punicalagin, and the ellagitannin extract in all the fecal cultures from different volunteers, but with very different production rates and concentrations. This large variability in the concentration of metabolite and kinetics of metabolite production is consistent with the large variability found in the excretion of these metabolites in urine in vivo after human consumption of ellagitannins, and with differences in the composition of the fecal microflora. No correlation between isoflavone and ellagic acid metabolism by fecal microflora was observed. The present study confirms the microbial origin of the recently reported in vivo generated hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives in humans and is a further step in the study of the bioavailability and metabolism of ellagic acid and ellagitannins.     

Antiproliferative effects of carotenoids extracted from Chlorella ellipsoidea and Chlorella vulgaris on human colon cancer cells

The antiproliferative activity of carotenoids separated from marine Chlorella ellipsoidea and freshwater Chlorella vulgaris has been evaluated. HPLC analysis revealed that the main carotenoid from C. ellipsoidea was composed of violaxanthin with two minor xanthophylls, antheraxanthin and zeaxanthin, whereas the carotenoid from C. vulgaris was almost completely composed of lutein. In an MTT assay, both semipurified extracts of C. ellipsoidea and C. vulgaris inhibited HCT116 cell growth in a dose-dependent manner, yielding IC(50) values of 40.73 +/- 3.71 and 40.31 +/- 4.43 microg/mL, respectively. In addition, treatment with both chlorella extracts enhanced the fluorescence intensity of the early apoptotic cell population in HCT116 cells. C. ellipsoidea extract produced an apoptosis-inducing effect almost 2.5 times stronger than that of the C. vulgaris extract. These results indicate that bioactive xanthophylls of C. ellipsoidea might be useful functional ingredients in the prevention of human cancers.     

稻-麦轮作条件下不同施肥模式土壤水溶性氮的变化与籽粒产量的关系

肥料用量、肥料种类和施肥方式直接影响土壤供氮强度和作物的正常生长发育.通过田间试验,研究减量施用氮、磷肥,增加钾肥投入时土壤水溶性氮含量的变化与水稻、小麦籽粒产量的关系.试验设置5个处理:不施肥(CK)、习惯施肥(FP)、推荐施肥(LRF)、商品有机肥部分替代化肥(RF-OM)、秸秆部分替代化肥(RF-S),各处理重复...     

Synergistic inhibition of the growth of suspension cultured tobacco cells by simultaneous treatment with cadmium and arsenic in relation to phytochelatin synthesis

Simultaneous treatments with Cd and arsenic (arsenite and arsenate) led to the synergistic growth inhibition of tobacco (Nicotiana tabacum cv. BY-2) cells. Cd contents in cells increased by co-treatment with arsenic for 24 h. The amount of total phytochelatins (PCs) per unit of Cd in the cells treated with Cd and arsenate was lower than that in the cells treated with Cd alone. Simultaneous treatments with Cd and arsenic promoted the induction of the biosynthesis of (γ-Glu-Cys)₂-Gly and inhibited the induction of the biosynthesis of (γ-GluCys)₃-Gly and (γ-Glu-Cys)₄-Gly, compared with the treatment with Cd alone. Consequently, since the inhibition of PC biosynthesis led to the increase of the cellular concentration of putative ionic (= toxic) Cd, cell growth was inhibited synergistically by simultaneous treatments with Cd and arsenic. In addition, based on the results showing that buthionine sulfoximine increased the sensitivity to arsenite and arsenate, that PC biosynthesis was induced by treatment with arsenite or arsenate, it is suggested that glutathione and/or its metabolic products such as PCs are involved in arsenic tolerance.     

Induction of apoptosis in cancer cells by Bilberry (Vaccinium myrtillus) and the anthocyanins

Among ethanol extracts of 10 edible berries, bilberry extract was found to be the most effective at inhibiting the growth of HL60 human leukemia cells and HCT116 human colon carcinoma cells in vitro. Bilberry extract induced apoptotic cell bodies and nucleosomal DNA fragmentation in HL60 cells. The proportion of apoptotic cells induced by bilberry extract in HCT116 was much lower than that in HL60 cells, and DNA fragmentation was not induced in the former. Of the extracts tested, that from bilberry contained the largest amounts of phenolic compounds, including anthocyanins, and showed the greatest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Pure delphinidin and malvidin, like the glycosides isolated from the bilberry extract, induced apoptosis in HL60 cells. These results indicate that the bilberry extract and the anthocyanins, bearing delphinidin or malvidin as the aglycon, inhibit the growth of HL60 cells through the induction of apoptosis. Only pure delphinidin and the glycoside isolated from the bilberry extract, but not malvidin and the glycoside, inhibited the growth of HCT116 cells.     

Cellular uptake and efflux of trans-piceid and its aglycone trans-resveratrol on the apical membrane of human intestinal Caco-2 cells

Two stilbenes (trans-piceid and its aglycone trans-resveratrol) were investigated in the uptake across the apical membrane of the human intestinal cell line Caco-2 in order to determine their mechanisms of transport. The uptake was quantified using a reverse phase high-performance liquid chromatography method with fluorescence detection. The rate of cellular accumulation in the cells was found to be higher for trans-resveratrol than for trans-piceid. In addition, trans-resveratrol uses passive transport to cross the apical membrane of the cells, whereas the transport of trans-piceid is likely active. With regard to the mechanisms of transport, the involvement of the active transporter SGLT1 in the absorption of trans-piceid was deduced using various inhibitors directly or indirectly exploiting the activity of this transporter (glucose, phlorizin, and ouabain). Moreover, we investigated the involvement of the multidrug-related protein 2 (MRP2), an efflux pump present on the apical membrane, in stilbene efflux by Caco-2 cells. The effect of MK-571 (an MRP inhibitor) seems to implicate MRP2 as responsible for apical efflux of trans-piceid and trans-resveratrol.     

Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries

The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41-63% (average 53%) inhibition compared to controls for the HT29 cells and 26-56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds.     

Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells

As part of an effort to improve plant-derived foods such as potatoes, eggplants, and tomatoes, the antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells of a series of structurally related individual compounds were examined using a microculture tetrazolium (MTT) assay. The objective was to assess the roles of the carbohydrate side chain and aglycon part of Solanum glycosides in influencing inhibitory activities of these compounds. Evaluations were carried out with four concentrations each (0.1, 1, 10, and 100 microg/mL) of the the potato trisaccharide glycoalkaloids alpha-chaconine and alpha-solanine; the disaccharides beta(1)-chaconine, beta(2)-chaconine, and beta(2)-solanine; the monosaccharide gamma-chaconine and their common aglycon solanidine; the tetrasaccharide potato glycoalkaloid dehydrocommersonine; the potato aglycon demissidine; the tetrasaccharide tomato glycoalkaloid alpha-tomatine, the trisaccharide beta(1)-tomatine, the disaccharide gamma-tomatine, the monosaccharide delta-tomatine, and their common aglycon tomatidine; the eggplant glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine. All compounds were active in the assay, with the glycoalkaloids being the most active and the hydrolysis products less so. The effectiveness against the liver cells was greater than against the colon cells. Potencies of alpha-tomatine and alpha-chaconine at a concentration of 1 microg/mL against the liver carcinoma cells were higher than those observed with the anticancer drugs doxorubicin and camptothecin. Because alpha-chaconine, alpha-solanine, and alpha-tomatine also inhibited normal human liver HeLa (Chang) cells, safety considerations should guide the use of these compounds as preventative or therapeutic treatments against carcinomas.     

Pyrrolidine dithiocarbamate inhibition of luteolin-induced apoptosis through up-regulated phosphorylation of Akt and caspase-9 in human leukemia HL-60 cells

Previously, we observed that luteolin effectively inhibited cell growth and induced apoptosis in HL-60 cells. In that study, we also explored the modulatory effects and molecular mechanisms of pyrrolidine dithiocarbamate (PDTC) on the cytotoxicity of luteolin to HL-60 cells. In this study, we found that PDTC was able to inhibit luteolin-induced cell apoptosis in a dose-dependent manner. When HL-60 cells were treated with PDTC for 0.5 h before 60 microM luteolin treatment, the DNA ladder disappeared. Moreover, flow cytometry showed that PDTC had dose dependently decreased the percentage of apoptotic HL-60 cells and had not interfered with luteolin's ability to change the mitochondrial membrane potential or its ability to trigger the release of cytochrome c to cytosol. Detection by Western blotting, however, did show that PDTC had interfered with luteolin's ability to cleave poly(ADP-ribose)polymerase and DNA fragmentation of factor-45. Three hours after the PDTC-pretreated HL-60 cells were treated with 60 microM luteolin, the product cleaved from Akt started to appear. Therefore, not only was PDTC able to stop the apoptosis of HL-60 cells treated with luteolin, it was also found to increase phosphorylation of Akt and caspase-9. These results suggest that in the luteolin-induced apoptotic pathway, phosphorylation of procaspase-9 by survival signals might play an important role in the ultimate fate of HL-60 cells.     

Antitumor activity of capsaicin on human colon cancer cells in vitro and colo 205 tumor xenografts in vivo

Capsaicin was reported to inhibit cancer cell growth. The aim of this study was to evaluate the antitumor potential of capsaicin by studying antitumor activity in vitro as well as in vivo. The in vitro studies are to examine the effects of capsaicin on human colon cancer colo 205 cells after exposure to capsaicin. The results showed that capsaicin induced cytotoxic effects in a time- and dose-dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but decreased the level of mitochondrial membrane potential (ΔΨ(m)) in colo 205 cells. Data from Western blotting analysis indicated that the levels of Fas, cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the levels of pro-apoptotic proteins such as Bax. Capsaicin-induced apoptosis in colo 205 cells was also done through the activations of caspase-8, -9 and -3. In vivo studies in immunodeficient nu/nu mice bearing colo 205 tumor xenografts showed that capsaicin effectively inhibited tumor growth. The potent in vitro and in vivo antitumor activities of capsaicin suggest that capsaicin might be developed for the treatment of human colon cancer.     

Monascuspiloin induces apoptosis and autophagic cell death in human prostate cancer cells via the Akt and AMPK signaling pathways

Monascus pigments have been reported to possess anticancer effects in various cancer cells; however, the molecular mechanisms of their anticancer properties remain largely unknown. Monascuspiloin is an analogue of the Monascus pigment monascin, and its anticancer growth activity against human prostate cancer cells was evaluated using in vitro and in vivo models. Monascuspiloin effectively inhibits the growth of both androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. Monascuspiloin preferentially induces apoptosis in LNCaP cells by attenuating the PI3K/Akt/mTOR pathway. In androgen-independent PC-3 cells, monascuspiloin induces G2/M arrest and autophagic cell death by an AMPK-dependent pathway. Induction of autophagy in PC-3 cells further sensitizes cells to apoptosis induced by monascuspiloin. Monascuspiloin inhibits tumor growth in nude mice bearing PC-3 xenografts through induction of apoptosis and autophagy. This study is the first to demonstrate that monascuspiloin has therapeutic potential for the treatment of both androgen-dependent and -independent human prostate cancers.     

Relative inhibition of lipid peroxidation, cyclooxygenase enzymes, and human tumor cell proliferation by natural food colors

The most abundant water soluble natural food colors are betacyanins and anthocyanins. Similarly, lycopene, bixin, beta-carotene, and chlorophyll are water insoluble colors. Pure betanin, bixin, lycopene, chlorophyll, beta-carotene, and cyanidin-3-O-glucoside were isolated from Beta vulgaris, Bixa orellana,Lycopersicum esculentum, Spinacia oleracea, Daucus carrota, and Prunus cerasus, respectively. These natural pigments, alone and in combination, were evaluated for their relative potencies against cyclooxygenase enzymes and tumor cell growth inhibition by using MCF-7 (breast), HCT-116 (colon), AGS (stomach), CNS (central nervous system), and NCI-H460 (lung) tumor cell lines. Among the colors tested, betanin, cyanidin-3-O-glucoside, lycopene, and beta-carotene inhibited lipid peroxidation. However, all pigments tested gave COX-1 and COX-2 inhibition and showed a dose-dependent growth inhibition against breast, colon, stomach, central nervous system, and lung tumor cells, respectively. The mixtures of these pigments were also evaluated for their synergistic effects and chemical interactions at various concentrations. The mixture of anthocyanin and betanin negated their efficacy in the cell growth inhibitory assay and did not enhance the COX enzyme inhibitory activity. This is the first report of a comparative evaluation and the impact on biological activities of these pigments alone and in combination.     

Cancer chemopreventive effects of lycopene: suppression of MMP-7 expression and cell invasion in human colon cancer cells

Clinical studies indicate that high blood levels of leptin or matrix metalloproteinase-7 (MMP-7; matrilysin) proteins are associated with tumor progression of human colorectal cancer (CRC). Leptin could play an important role in cell migration and invasion of cancer cells. Our previous study indicated that lycopene could inhibit the proliferation of human colon cancer cells in vitro. However, the inhibitory effects of lycopene on the progression of human colon cancer cells have not been demonstrated yet. In this study, we investigated the inhibitory effects of lycopene on tumor progression including cell invasion and MMP-7 expression in leptin-stimulated human colon cancer cells in vitro. Our results demonstrated that lycopene significantly inhibited leptin-mediated cell invasion and MMP-7 expression in human colon cancer HT-29 cells. Lycopene could augment the expression and stability of E-cadherin proteins. Our results showed that MAPK/ERK and PI3K/Akt signaling pathways played important roles in leptin-mediated MMP-7 expression and cell invasion. Lycopene could effectively inhibit the phosphorylation of Akt, glycogen synthase kinase-3β (GSK-3β) and ERK 1/2 proteins. The molecular mechanisms of lycopene were in part through decreases in nuclear levels of AP-1 and β-catenin proteins. These novel findings suggested that lycopene could act as a chemopreventive agent to suppress MMP-7 expression and leptin-mediated cell invasion in human colon cancer HT-29 cells.