Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells

High consumption of soy isoflavones in Asian diets has been correlated with a lower incidence of clinically important cases of prostate cancer. The chemopreventive properties of these diets may result from an interaction of several types of isoflavones, including genistein and daidzein. The present study investigated the effects of a soy isoflavone concentrate (ISF) on growth and gene expression profiles of PC-3 human prostate cancer cells. Trypan blue exclusion and [3H]-thymidine incorporation assays showed that ISF decreased cell viability and caused a dose-dependent inhibition of DNA synthesis, respectively, with 50% inhibition (IC50) of DNA synthesis at 52 mg/L (P = 0.05). The glucoside conjugates of genistein and daidzein in ISF were converted to bioactive free aglycones in cell culture in association with the inhibition of DNA synthesis. Flow cytometry and Western immunoblot analyses showed that ISF at 200 mg/L caused an accumulation of cells in the G2/M phase of the cell cycle (P < 0.05) and decreased cyclin A by 20% (P < 0.05), respectively. The effect of ISF on the gene expression profile of PC-3 cells was analyzed using Affymetrix oligonucleotide DNA microarrays that interrogate approximately 17,000 human genes. Of the 75 genes altered by ISF, 28 were upregulated and 47 were downregulated (P < 0.05). Further analysis showed that IL-8, matrix metalloproteinase 13, inhibin beta A, follistatin, and fibronectin mRNA levels were significantly reduced, whereas the expression of p21(CIP1), a major cell cycle inhibitory protein, was increased. The effects of ISF on the expression of IL-8 and p21(CIP1) mRNA and protein were validated at high and low ISF concentrations. Our data show that ISF inhibits the growth of PC-3 cells through modulation of cell cycle progression and the expression of genes involved in cell cycle regulation, metastasis, and angiogenesis.     

The antiproliferative effect of dietary fiber phenolic compounds ferulic acid and p-coumaric acid on the cell cycle of Caco-2 cells

Epidemiological and animal studies have shown that dietary fiber is protective against the development of colon cancer. Dietary fiber is a rich source of the hydroxycinnamic acids ferulic acid (FA) and p-coumaric acid (p-CA), which both may contribute to the protective effect. We have investigated the effects of FA and p-CA treatment on global gene expression in Caco-2 colon cancer cells. The Caco-2 cells were treated with 150 μM FA or p-CA for 24 h, and gene expression was analyzed with cDNA microarray technique. A total of 517 genes were significantly affected by FA and 901 by p-CA. As we previously have found that FA or p-CA treatment delayed cell cycle progression, we focused on genes involved in proliferation and cell cycle regulation. The expressions of a number of genes involved in centrosome assembly, such as RABGAP1 and CEP2, were upregulated by FA treatment as well as the gene for the S phase checkpoint protein SMC1L1. p-CA treatment upregulated CDKN1A expression and downregulated CCNA2, CCNB1, MYC, and ODC1. Some proteins corresponding to the affected genes were also studied. Taken together, the changes found can partly explain the effects of FA or p-CA treatment on cell cycle progression, specifically in the S phase by FA and G(2)/M phase by p-CA treatment.     

Caffeine Overcomes Genistein-Induced G2/M Cell Cycle Arrest in Breast Cancer Cells

Although inhibition of tumor cell growth by genistein is mediated by different types of cell cycle arrest, its regulation of genes related to the cell cycle is not clear. In this study, genistein caused a concentration-dependent growth inhibition in the hormone-independent cell line MDA-MB-435S. Flow cytometric analysis showed that genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. Caffeine enhanced the inhibition of cell proliferation induced by genistein. Caffeine alone did not have an appreciable effect on the phases of the cell cycle, but caffeine at 3 mM completely eliminated genistein-induced G2/M cell cycle arrest. cDNA microarrays were used to investigate the mechanism of genistein-induced, caffeine-negated G2/M arrest. We identified 12 genes, which had opposite responses to genistein and caffeine treatments. Among these, 5 genes were upregulated by genistein and downregulated by caffeine; 7 genes were downregulated by genistein and upregulated by caffeine. Reversal by caffeine of genistein-induced G2/M phase arrest in breast cancer cell lines could increase their sensitivity to genistein and enhance genistein-induced inhibition of cell growth. Genes that have opposite responses to genistein and caffeine may be involved in regulation of the G2/M phase of the cell cycle.     

Caffeine overcomes genistein-induced G2/M cell cycle arrest in breast cancer cells

Although inhibition of tumor cell growth by genistein is mediated by different types of cell cycle arrest, its regulation of genes related to the cell cycle is not clear. In this study, genistein caused a concentration-dependent growth inhibition in the hormone-independent cell line MDA-MB-435S. Flow cytometric analysis showed that genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. Caffeine enhanced the inhibition of cell proliferation induced by genistein. Caffeine alone did not have an appreciable effect on the phases of the cell cycle, but caffeine at 3 mM completely eliminated genistein-induced G2/M cell cycle arrest. cDNA microarrays were used to investigate the mechanism of genistein-induced, caffeine-negated G2/M arrest. We identified 12 genes, which had opposite responses to genistein and caffeine treatments. Among these, 5 genes were upregulated by genistein and downregulated by caffeine; 7 genes were downregulated by genistein and upregulated by caffeine. Reversal by caffeine of genistein-induced G2/M phase arrest in breast cancer cell lines could increase their sensitivity to genistein and enhance genistein-induced inhibition of cell growth. Genes that have opposite responses to genistein and caffeine may be involved in regulation of the G2/M phase of the cell cycle.     

How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8?%) for 72?h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2'-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.     

Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells

We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO(2)-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED(50)) was 70 microg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED(50) = 250 g/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G(2)/M cells (P <.05) by treatment with Oil (35 microg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 microg/mL) resulted in significant 2.3 +/- 0.001-fold (mean +/- SEM) up-regulation of the cyclin-dependent kinase inhibitor p21((waf1/cip1)) (P <.01) and 0.6 +/- 0.14-fold down-regulation of c-myc (P <.05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.     

Lycopene differentially induces quiescence and apoptosis in androgen-responsive and -independent prostate cancer cell lines

BACKGROUND & AIMS: Lycopene has been credited with a number of health benefits including a decrease in prostate cancer risk. Our study investigates the molecular mechanism underlying anti-cancer activity of lycopene-based products in androgen-responsive (LNCaP) and androgen-independent (PC3) cells. METHODS: The effect of lycopene-based agents on prostate cancer growth and survival were examined using proliferation assays, bromodeoxyuridine incorporation and flow cytometric analysis of cellular DNA content. Biochemical effects of lycopene treatment were investigated by immunoblotting for changes in the absolute levels and phosphorylation states of cell cycle regulatory and signalling proteins. RESULTS: LNCaP and PC3 cells treated with the lycopene-based agents undergo mitotic arrest, accumulating in G0/G1 phase. Immunoblot screening indicated that lycopene's antiproliferative effects are likely achieved through a block in G1/S transition mediated by decreased levels of cyclins D1 and E and cyclin dependent kinase 4 and suppressed Retinoblastoma phosphorylation. These responses correlated with decreased insulin-like growth factor-I receptor expression and activation, increased insulin-like growth factor binding protein 2 expression and decreased AKT activation. Exposure to lycopene at doses as low as 10 nM for 48 h induced a profound apoptotic response in LNCaP cells. In contrast PC3 cells were resistant to apoptosis at doses up to 1 microM. CONCLUSIONS: Lycopene exposure can suppress phosphatidylinositol 3-kinase-dependent proliferative and survival signalling in androgen-responsive LNCaP and androgen-independent PC3 cells suggesting that the molecular mechanisms for the cytostatic and cytotoxic actions of lycopene involve induction of G0/G1 cell cycle arrest. This study supports further examination of lycopene as a potential agent for both the prevention and treatment of prostate cancer.     

Expression profile of apoptosis related genes and radio-sensitivity of prostate cancer cells

Radio-resistant or recurrent prostate cancer represents a serious health risk for approximately 20%-30% of patients treated with primary radiation therapy for clinically localized prostate cancer. In the present study, we investigated the expression profiles of 84 genes involved in various apoptosis pathways in two prostate cancer cell lines LNCaP (P53+ and AR+) and PC3 (P53- and AR-). We also studied the effect of monensin, an apoptosis inducing reagent, in X-ray-induced cell killing. Comparison of gene expressions between unirradiated LNCaP and PC3 cells revealed distinguished gene expression patterns. The data showed a significantly higher expression level of genes involved in the caspase/card family and the TNF ligand/receptor family in PC3 cells, whereas, LNCaP cells exhibited higher expressions in the p53 related genes. At 2 and 4 hrs post a 10 Gy X-ray exposure, changes of gene expressions were detected in a significant fraction of the genes in LNCaP cells, but no significant changes were found in PC3 cells. There was no significant apoptosis-inducing effect of X-rays (up to 10 Gy) in both cell lines; however, monensin was shown to be effective in inducing apoptosis in LNCaP, but not in PC3 cells. In addition, the effect of combined treatment of monensin and X-rays in LNCaP cells appeared to be synergistic. Our results suggest that monensin may be effective for both cancer cell killing and radiosensitizing, and the different expression profiles in apoptosis related genes in cancer cells may be correlated with their sensitivity to apoptosis inducing reagents.     

Molecular mechanism of anti-prostate cancer activity of Scutellaria baicalensis extract

Scutellaria baicalensis is a widely used Chinese herbal medicine historically used in antiinflammatory and anticancer therapy. The goals of the study were to 1) determine its in vitro and in vivo anti-prostate cancer activity, 2) investigate its molecular mechanism directed at cell proliferation control including cyclooxygenase-2(COX-2) prostaglandin E2 (PGE2) and cyclins/cdks pathways, and 3) compare it with those of PC-SPES (PC stands for prostate cancer and spes is Latin for hope), a former herbal mixture for prostate cancer treatment of which S. baicalensis is a major constituent. Two human prostate cancer cell lines (LNCaP, androgen dependent, and PC-3, androgen independent) were assessed for growth inhibition. S. baicalensis exerted dose- and time-dependent increased growth inhibition in both cell lines. However, the PC-3 cells IC50 (50% growth inhibition concentration) were slightly more sensitive than LNCaP cells (IC50=0.15 mg/ml), although the former is androgen independent. S. baicalensis was more effective in inhibition of cell growth compared with PC-SPES (IC50=0.38 mg/ml for PC-3 cells). Significant reduction of PGE2 synthesis in both cells after treatment with S. baicalensis resulted from direct inhibition of COX-2 activity rather than COX-2 protein suppression. S. baicalensis also inhibited prostate-specific antigen production in LNCaP cells. Finally, S. baicalensis suppressed expression of cyclin D1 in LNCaP cells, resulting in a G1 phase arrest, while inhibiting cdk1 expression and kinase activity in PC-3 cells, ultimately leading to a G2/M cell cycle arrest. Animal studies showed a 50% reduction in tumor volume after a 7-wk treatment period. This study demonstrated that S. baicalensis may be a novel anticancer agent for the treatment of prostate cancer.     

Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression

Cyclooxygenase (COX) inhibitors have suppressive effects on several types of cancer cells including prostate cancer. In this study, we considered the potential COX-inhibitory activity of a unique anti-inflammatory herbal preparation (Zyflamend; New Chapter, Inc., Brattleboro, VT) and analyzed its effects on the human prostate cancer cell line LNCaP. COX inhibitory activity of Zyflamend was determined by a spectrophotometric-based assay using purified ovine COX-1 and COX-2 enzymes. Effects of Zyflamend on LNCaP cell growth and apoptosis in vitro were assessed by cell counting, Western blot detection of poly ADP-ribose polymerase (PARP) cleavage, and measurement of caspase-3 activity in treated and control cell extracts. Western blotting techniques were conducted to determine the effects of this herbal preparation on the expression of the cell signaling proteins, p21, androgen receptor (AR), phospho-protein kinase C (pPKC)(alpha/beta), and phospho (p)Stat3. The phospohorylation status of several signal transduction phosphoproteins was profiled using a high-throughput phosphoprotein screening assay in treated cells and compared to controls. Zyflamend dramatically decreased COX-1 and COX-2 enzymatic activity. Elevated p21 expression coincided with attenuated cell growth following treatment of LNCaP cells with Zyflamend. PARP cleavage fragments were evident, and caspase-3 activity was upregulated over the control indicating the ability of Zyflamend to induce apoptosis of these cells. Androgen receptor expression levels declined by 40%, and decreases were observed in the active forms of Stat3 and PKC(alpha/beta) in Zyflamend-treated LNCaP cells. Zyflamend inhibited both COX-1 and COX-2 enzymatic activities, suppressed cell growth, and induced apoptosis in LNCaP cells. However, our data suggests that the effects are likely due to COX-independent mechanisms potentially involving enhanced expression of p21 and reduced expression of AR, pStat3, and pPKC(alpha/beta).     

Changes in cell cycle and extracellular matrix gene expression during placental development in deer mouse (Peromyscus) hybrids

Crosses between two species of the rodent genus Peromyscus produce defects in both growth and development. The defects are pronounced in the hybrid placentas. Peromyscuys maniculatus (strain BW) females mated to P. polionotus (strain PO) males produce placentas half the size of the parental species, as well as growth-retarded embryos. In contrast, PO females mated to BW males result in defective conceptuses that display embryonic and placental overgrowth. These 'parent-of-origin'-dependent phenotypes are consistent with previous studies that demonstrated altered expression of imprinted genes and genetic linkage of the overgrowth phenotypes to imprinted domains. In the present study, we take a broader approach in assessing perturbations in hybrid placental gene expression through the use of Mus musculus cDNA microarrays. In verifying classes of genes identified in microarray screens differentially regulated during hybrid placental development, we focused on those influencing the cell cycle and extracellular matrix (ECM). Our work suggests that cell cycle regulators at the G(1)/S phase check-point are downregulated in the large hybrid placenta, whereas the small hybrid placenta is more variable. The ECM genes are typically downstream targets of cell cycle regulation and their misregulation is consistent with many of the dysmorphic phenotypes. Thus, these data suggest imbalances in proliferation and differentiation in hybrid placentation.     

Lycopene inhibits the growth of normal human prostate epithelial cells in vitro

Lycopene has repeatedly been shown to inhibit the growth of human prostate cells in vitro. However, previous studies with lycopene have focused on cancer specimens, and it is still unclear whether this carotenoid affects the growth of normal human prostate cells as well. Therefore, we investigated the effects of lycopene on normal human prostate epithelial cells (PrEC) by treating them with synthetic all-E-lycopene (up to 5 micromol/L) and assessing proliferation via [3H]thymidine incorporation. The effects of lycopene on cell cycle progression were investigated via flow cytometry. To elucidate whether lycopene modulates cyclins involved in cell cycle progression, protein expressions of cyclins D1 and E were analyzed. The results show that lycopene significantly inhibited the growth of PrEC in a dose-dependent fashion. Flow cytometry revealed a significant cell cycle arrest in the G0/G1 phase. This effect was confirmed by inhibition of cyclin D1 protein expression, whereas cyclin E levels remained unchanged. The results demonstrate that lycopene inhibits growth of nonneoplastic PrEC in vitro. We hypothesize that lycopene might likewise inhibit the growth of prostatic epithelial cells in vivo. This might have an effect on prostate development and/or on enlargement of prostate tissue as found in benign prostate hyperplasia, a potential precursor of prostate cancer.     

Potential in a single cancer cell to produce heterogeneous morphology, radiosensitivity and gene expression

Morphologically heterogeneous colonies were formed from a cultured cell line (KYSE70) established from one human esophageal carcinoma tissue. Two subclones were separated from a single clone (clone13) of KYSE70 cells. One subclone (clone13-3G) formed mainly mounding colonies and the other (clone 13-6G) formed flat, diffusive colonies. X-irradiation stimulated the cells to dedifferentiate from the mounding state to the flat, diffusive state. Clone 13-6G cells were more radiosensitive than the other 3 cell lines. Clustering analysis for gene expression level by oligonucleotide microarray demonstrated that in the radiosensitive clone13-6G cells, expression of genes involved in cell adhesion was upregulated, but genes involved in the response to DNA damage stimulus were downregulated. The data demonstrated that a single cancer cell had the potential to produce progeny heterogeneous in terms of morphology, radiation sensitivity and gene expression, and irradiation enhanced the dedifferentiation of cancer cells.     

Gene expression and cell cycle arrest in a rat keratinocyte line exposed to 56Fe ions

The purpose of the present work was to examine gene expression patterns in a rat keratinocyte line exposed to a (56)Fe ion beam. The cells were exposed to 1.01 geV/nucleon (56)Fe ions generated by the NASA Space Radiation Laboratory facility. Data from Affymetrix rat microarrays (RAT 230_2) were processed by BRB ArrayTools 3.3.0 software, and the Gene Ontogeny (GO) database was utilized to categorize significantly responding genes. Cell cycle distribution was analyzed by flow cytometry, and cell survival was based on the colony survival assay. At 24 h after 3.0 Gy of (56)Fe ion radiation, 69 known genes were significantly (p 相似文献   

佛波酯对BALB/c 3T3细胞转化早期基因表达的影响

目的 探讨佛波酯(12-O-tetradecanoylphorbol-13-acetate,TPA)促进细胞转化早期基因表达谱的变化。方法 以N-甲基-N’-硝基-N-亚硝基胍(N-methyl-N’-nitro-N-nitrosoguanidine,MNNG)为启动剂,TPA为促癌剂,建立BALB／c3T3细胞转化模型。采用锥虫蓝染色法检测细胞生长情况,流式细胞仪检测细胞周期变化。采用cDNA微阵列检测TPA处理早期的基因表达谱变化。结果 TPA处理早期可抑制细胞增殖,阻滞细胞于G1期与S期。TPA处理4h和24h后,在检测的1152个基因中筛选出19个差异表达基因,其中9个基因表达上调,10个基因表达下调。许多差异表达基因的功能与细胞增殖、凋亡和周期调控相关,主要涉及ras和p53基因信号传导通路。结论 TPA在促进BALB／c3T3细胞转化的早期阶段,可影响某些调节细胞周期进展基因的转录表达,从而导致细胞生长阻滞。     

Anti-apoptotic action of zearalenone in MCF-7 cells

Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin, is present in high concentrations in dairy products and cereals. Studies have indicated that ZEA could strongly provoke proliferation in estrogen-dependent breast cancer MCF-7 cells following estrogen ablation. The current study confirmed the previous studies that within the range of concentrations of 2-96nM, like endogenous estradiol, ZEA could stimulate proliferation in MCF-7 cells with inducing a profound increase in S phase and a modest increase in G(2)/M phase that was accompanied by a decrease in G(0)/G(1) phase. The Cell Death Detection ELISA was used to determine whether the robust cell viability retrieved by ZEA was a result of inhibited apoptosis. Data indicated that ZEA-mediated inhibition of apoptosis is significantly evident (P<0.05) and in a dose-dependent manner. Western blot and multiple RT-PCR analysis revealed that the anti-apoptotic bcl-2 was upregulated at both protein and mRNA levels, together with the downregulation of pro-apoptotic bax. In short, the results here showed that ZEA possessed comparative estrogenic activity and could promote the progression of MCF-7 cells through the cell cycle by a decrease in G(0)/G(1) phase and a significant increase in S phase. The pro-proliferative activity of ZEA was due to inhibition of apoptosis through regulation of bax/bcl-2 expression. Therefore, we conclude that contamination of ZEA in food might contribute to the increasing incidence rates of breast cancer.     

Effects of Selenite and Genistein on G2/M Cell Cycle Arrest and Apoptosis in Human Prostate Cancer Cells

Combination of chemopreventive agents with distinct molecular mechanisms is considered to offer a potential for enhancing cancer prevention efficacy while minimizing toxicity. Here we report two chemopreventive agents, selenite and genistein, that have synergistic effects on apoptosis, cell cycle arrest, and associated signaling pathways in p53-expressing LNCaP and p53-null PC3 prostate cancer cells. We show that selenite induced apoptosis only, whereas genistein induced both apoptosis and G ₂ /M cell cycle arrest. Combination of these two agents exhibited enhanced effects, which were slightly greater in LNCaP than PC3 cells. Selenite or genistein alone upregulated protein levels of p53 in LNCaP cells only and p21 ^waf1 and Bax in both cell lines. Additionally, genistein inhibited AKT phosphorylation. Downregulation of AKT by siRNA caused apoptosis and G ₂ /M cell cycle arrest and masked the effects of genistein. Treatment with insulin-like growth factor I (IGF-I) elevated levels of total and phosphorylated AKT and suppressed the effects of genistein. Neither downregulation of AKT nor IGF-I treatment altered the cellular effects of selenite. Our study demonstrates that selenium and genistein act via different molecular mechanisms and exhibit enhanced anticancer effects, suggesting that a combination of selenium and genistein may offer better efficacy and reduction of toxicity in prostate cancer prevention.     

Reduced growth and integrin expression of prostate cells cultured with lycopene, vitamin E and fish oil in vitro

Integrins are transmembrane proteins that facilitate the interaction of cells with the extracellular environment. They have also been implicated in cancer progression. The effects of nutrients thought to be involved in the prevention of prostate cancer on integrin expression have not been determined. Prostate cancer cell lines representing a range of malignancy from normal (RWPE-1) to highly invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene (10 nM), vitamin E (5 microm) or fish oil (100 microm) for 48 h. Growth and integrin (alpha2beta1, alphavbeta3 and alphavbeta5) expression were assessed using Trypan Blue exclusion and monoclonal antibodies combined with flow cytometry. Vitamin E enhanced (P < 0.001) whereas fish oil reduced the growth of all the cell lines tested (P < 0.001). Lycopene had no effect on growth. All the malignant cell lines exhibited lower expression of alpha2beta1 with the addition of lycopene to culture media. Supplemental fish oil reduced alpha2beta1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins alphavbeta3 and alphavbeta5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.