枸杞多糖对人前列腺癌细胞生长影响

目的 观察枸杞多糖对体外培养的雄激素非依赖型人前列腺癌PC-3细胞存活率、细胞周期及其凋亡的影响。方法 用四甲基偶氮噻唑蓝（MTT）法检测枸杞多糖对PC-3细胞作用的时间效应和剂量效应，并计算细胞生长抑制率；流式细胞仪观察枸杞多糖处理PC-3细胞后细胞周期以及细胞凋亡的改变。结果 枸杞多糖对PC-3细胞的增殖有明显的抑制作用，抑制率可达87．84％，且呈剂量-效应和时间-效应关系；流式细胞仪分析显示。枸杞多糖可影响该细胞周期并引起细胞凋亡，凋亡率高达40％。结论 枸杞多糖对人前列腺癌PC-3细胞的生长有明显抑制作用，其机制可能是通过诱导人前列腺癌细胞凋亡和影响其生长周期而实现。     

染料木黄酮抑制DU145细胞的作用及其机制研究

目的: 研究大豆异黄酮主要成分染料木黄酮 (GEN)对离体培养DU145前列腺癌细胞的生长抑制作用及其机制。方法: DU145前列腺癌细胞接受不同浓度的GEN处理,克隆形成试验用于测定DU145细胞的生存曲线及IC50;DNA ladder和DAPI(4-6-二氨基-2-苯基吲哚)染色法用于检测细胞凋亡;流式细胞仪和免疫印迹法分别用于观察细胞周期改变和相关蛋白表达。结果: 克隆形成试验显示: GEN能抑制离体培养DU145细胞的生长,其作用于DU145细胞的IC50约为30 mmol。GEN 处理24h后,早发细胞凋亡仅见于高浓度GEN处理组,72 h后凋亡亦见于较低浓度GEN组。流式细胞仪显示GEN可导致DU145细胞G2/M期阻滞;细胞周期相关蛋白分析显示随着GEN浓度的提高,p21cip1蛋白表达稳步上升,周期素B1呈双相改变,cdc-2则变化较小。结论: GEN可抑制离体培养DU145前列腺癌细胞的生长,其作用机制可能与GEN诱导细胞凋亡和细胞周期阻滞有关,后者同时伴有细胞周期相关蛋白表达的改变。     

番茄红素对前列腺癌细胞PC-3增殖和细胞周期的影响

目的研究番茄红素对体外培养的雄激素非依赖性前列腺癌细胞PC-3的抑制作用及其可能的作用机制。方法采用MTT法和H3-TdR掺入法观察番茄红素对癌细胞增殖的影响,流式细胞仪观察同步化的细胞经番茄红素作用后细胞周期及凋亡的变化,RT-PCR检测cyclin D1、bcl-2、bax的mRNA的表达的变化。结果番茄红素抑制PC-3细胞的增殖和DNA合成、诱导其凋亡、改变细胞周期分布(使G0/G1期细胞增多、而S期和G2/M期细胞减少)。RT-PCR结果显示,cyclin D1和bcl-2的mRNA表达水平下调,而bax的mRNA表达水平上调。上述作用呈剂量效应关系。结论番茄红素可诱导PC-3细胞凋亡、改变细胞周期分布、影响cyclin D1、bcl-2、bax的mRNA的表达,从而抑制肿瘤细胞增殖。     

类胡萝卜素对人乳腺癌细胞增殖及bcl-2基因表达的影响

目的 观察类胡萝卜素对人乳腺癌MCF－7细胞存活率、细胞周期和凋亡,以及对凋亡相关基因bcl－2的影响。方法 用MTT检测类胡萝卜素对MCF－7细胞作用的时间效应和剂量效应;流式细胞仪观察类胡萝卜素处理人乳腺癌细胞后细胞周期以及细胞凋亡的改变。用RT－PCR检测凋亡相关基因bcl－2的变化。结果 6种结构不同的类胡萝卜素对MCF－7乳腺癌细胞展现出不同的增殖抑制效果,60μmol／L的β－胡萝卡素和番茄红素在第4天的抑制率分别为88．4％和87．8％,而玉米黄素、角黄素、虾青素和玉米黄素双棕榈酸酯的抑制作用较弱。类胡萝卜素并不诱导87．8％,而玉米黄素、角黄素、虾青素和玉米黄毒素双棕榈酸酯的抑制作用较弱。类胡萝卜素并不诱导MCF－7细胞凋亡,番茄红素可阻滞细胞周期于G1／M,玉米黄素双棕榈酸酯可阻滞细胞周期于G0／G1期,而其他类胡萝卡素并不影响细胞周期。类胡萝卜素可不同程度地下调凋亡相关基因bcl－2mRNA的表达,bcl－2基因的下调与类胡萝卜素的抑制作用呈较明显的相关性。结论 类胡萝卜素可直接抑制人乳腺癌细胞MCF－7的增殖,不同结构的类胡萝卜素可能具有不同的抑制机制。     

曲古抑菌素A阻断Stat3信号通路诱导前列腺癌细胞凋亡的实验研究

目的本实验研究组蛋白去乙酰化酶抑制剂曲古抑菌素A(TSA)对前列腺癌细胞DU145的抑制作用及其对信号传导与转录激活因子3(Stat3)信号通路的影响。方法采用不同浓度的TSA处理DU145不同时间后,四氮甲基唑蓝比色法测定TSA对细胞活力的抑制效应;流式细胞仪分析细胞周期的改变;蛋白印迹实验检测细胞凋亡相关蛋白半胱氨酸蛋白酶(Caspase)家族的Caspase-8、Caspase-9、Caspase-3、二磷酸腺苷核糖多聚酶(PARP)及Stat3信号蛋白活性(phospho-Stat3)的变化。结果 TSA时间和剂量依赖性地抑制DU145细胞的增殖,TSA处理细胞24 h和48 h后,细胞生存率分别是85.7%和68.7%;细胞经TSA处理后,细胞形态和细胞周期均发生明显的变化,细胞周期被阻断在G0/G1期,其细胞百分比从55.6%增加到68.5%;Western blot检测结果显示,TSA作用DU145细胞后,Stat3信号蛋白的磷酸化水平下降,同时IL-6对Stat3的刺激诱导作用也被TSA所阻断;Caspase-8、Caspase-9、Caspase-3、PARP等凋亡蛋白被TSA诱导活化,并发生显著剪切。结论 TSA能够通过抑制Stat3信号通路的活性来诱导DU145细胞凋亡。     

乳胞素诱导前列腺癌细胞凋亡机制的初步研究

目的 探讨乳胞素在诱导前列腺癌细胞凋亡作用中与核转录因子(NF)-κ B活性的关系.方法 利用乳胞素作用两种前列腺癌细胞,设立培养液处理的空白对照组和乳胞素处理组,乳胞素处理组分别向两种细胞中加入浓度递增的乳胞素(0.5、1.0、2.0、4.0μmol/L),作用时间分别为8、16和24h.MTT法检测细胞生存率,利用酶联免疫吸附试验定量分析NF-κ B DNA结合活性,Western blot法检测NF-κB P65核蛋白表达,酶分析法测定caspase-3活性.结果 DU145细胞基础状态下NF-κB DNA结合活性强于LNCaP细胞(t=4.728,P=0.001),应用乳胞素作用24 h后,与空白对照组比较,不同浓度乳胞素处理组均观察到NF-κB DNA结合活性减少.随着乳胞素浓度增加,LNCaP细胞NF-κB p65核蛋白表达水平下调,而DU145细胞NF-κB P65核蛋白表达水平没有变化.DU145细胞基础状态下caspase-3活性强于LNCaP细胞(t=4.519,P=0.001),乳胞素作用24h 后,DU145和LNCaP细胞caspase-3活性均随乳胞素浓度增加升高(2.0μmol/L乳胞素处理组与1.0μmol/L乳胞素处理组比较,DU145细胞P=0.000,LNCaP细胞P=0.000).结论 乳胞素对不同前列腺癌细胞有不同杀伤作用,并与抑制NF-κB活性促进前列腺癌细胞凋亡相关,对激素非依赖性前列腺癌细胞还可能存在其他抗肿瘤细胞生存途径.     

多西紫杉醇和腺病毒介导NDRG2基因对人前列腺癌细胞株DU145的协同作用

目的 观察携带NDRG2基因的腺病毒(Ad-NDRG2)与多西紫杉醇(DT)联合给药对人前列腺癌细胞株DU145的抗肿瘤增效作用.方法 以Ad-NDRG2感染体外培养的DU145细胞,采用Western-blot方法检测CyclinD1、CyclinE、NDRG2蛋白表达水平的变化.流式细胞仪检测和MTT试验分析Ad-NDRG2给药后DU145细胞对DT敏感性的变化.建立裸鼠移植瘤模型,观察Ad-NDRG2与DT联合给药的体内抗肿瘤作用.结果 Ad-NDRG2感染后,DU145细胞中NDRG2表达明显增加,而CyclinD1和CyclinE表达水平降低.Ad-NDRG2协同10-7 mol/L以上浓度DT作用48h,可增强对DU145细胞的生长抑制作用(抑制率=41.8％,t=4.18,P＜0.01),增强诱导凋亡作用(凋亡率=32.4％,x2=11.66,P＜0.05),并且使DT所致的G2/M期细胞比例由50.2％变为23.6％,部分逆转了其G2/M期阻滞.动物实验表明:DT组、Ad-NDRG2组、Ad-NDRG2与DT联合给药组其移植瘤的抑瘤率分别为30.7％、28.2％和55.8％,两药相互作用指数(CDI)为0.89.结论 腺病毒介导NDRG2基因感染细胞后,增加了人前列腺癌DU145细胞在体内及体外对多西紫杉醇的敏感性.     

葡萄汁对人前列腺癌PC-3细胞增殖和凋亡的影响

目的:探讨葡萄汁对人前列腺癌PC-3细胞生长抑制的作用及其机制。方法:白藜芦醇及不同浓度葡萄汁作用于人前列腺癌PC-3细胞48h;采用生长曲线及噻唑蓝(MTT)法检测葡萄汁、白藜芦醇对人前列腺癌PC-3细胞的生长抑制作用,通过原位(缺口)末端标记法(TUNEL)观察凋亡细胞的形态结构变化,流式细胞仪检测细胞凋亡峰。结果:葡萄汁、白藜芦醇能显著抑制人前列腺癌PC-3细胞生长;TUNEL方法检测呈阳性;流式细胞仪分析图上出现典型的凋亡细胞峰。以上各指标中,葡萄汁随着浓度增大作用加强;低剂量组的作用比白藜芦醇组差,中、高剂量组的白藜芦醇浓度低,但作用比白藜芦醇组强。结论:葡萄汁对抗人前列腺癌PC-3细胞的作用,除白藜芦醇外,可能还存在其他抗癌成分的作用。葡萄汁、白藜芦醇对PC-3细胞生长抑制作用的机制可能与其诱导人前列腺癌PC-3细胞凋亡有关。     

洛伐他汀对人粒系白血病细胞生长的影响

目的观察洛伐他汀(Lovastatin)对体外培养的人粒系白血病细胞株HL-60生长的影响。方法采用四甲基偶氮唑蓝(MTT)检测、流式细胞仪分析等技术。结果洛伐他汀可显著抑制HL-60细胞的增殖．且呈剂量一效应关系。流式细胞仪分析结果显示：洛伐他汀不仅能影响该细胞周期进程而且可诱导该细胞凋亡。结论洛伐他汀可能通过影响细胞的生长周期和诱导细胞凋亡来抑制HL-60细胞的增殖。     

三羟异黄酮对人乳腺癌细胞增殖和细胞周期的影响

目的 观察三羟异黄酮对体外培养的人乳腺癌细胞MDA—MB—435S细胞存活率、细胞周期和凋亡的影响。方法 用噻唑蓝(MTT)法观察三羟异黄酮对MDA—MB—435S细胞生长的影响；流式细胞仪观察三羟异黄酮处理人乳腺癌细胞后细胞周期改变的剂量效应和时间效应；吖啶橙／溴乙锭染色法在荧光显微镜下观察三羟异黄酮对MDA—MB—435S细胞的凋亡作用。结果 随剂量增大和作用时间延长，三羟异黄酮对细胞增殖的抑制作用逐渐增强。同时可以阻滞细胞周期于G2—M期，而且随剂量的增大，作用时间的延长，阻滞作用也增强。经吖啶橙染色法于荧光显微镜下可见，随三羟异黄酮剂量增大，细胞凋亡也逐渐明显。结论 三羟异黄酮可抑制人乳腺癌细胞的增殖，其作用机制可能包括诱导细胞凋亡和G2—M期阻滞。     

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.     

Lycopene and Apo-12′-Lycopenal Reduce Cell Proliferation and Alter Cell Cycle Progression in Human Prostate Cancer Cells

Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8′-lycopenal, or apo-12′-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12′-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12′-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression.     

Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cancer cells

Lycopene is one of the major carotenoids and is found almost exclusively in tomatoes and tomato products. Since tomato consumption is associated with decreased risk of prostate cancer, characterizing the effects of lycopene on cell growth or survival, cell cycle progression, and apoptosis in LCNaP human prostate cancer cells might elucidate the mechanisms of actions of lycopene. To discover the possible anti-cancer mechanism of lycopene, water-soluble lycopene was used, and cell cycle arrest and apoptosis were measured. Placebo formulation at each lycopene dose at 0.1, 1, and 5 microM was used as a control. After 6, 24, and 48 hours of incubation, cells were harvested and measured for cell viability. Lycopene at 1 microM inhibited cell growth by 31%, compared with its placebo formulation after a 48-hour incubation. Lycopene at 5 microM increased the number of cells in the G(2)/M phase of the cell cycle from 13% to 28% and decreased S-phase cells from 45% to 29%, while no shifts in cell cycle were detected in placebo-treated groups. Apoptosis was observed at the 5 microM lycopene formulation at the late stages during the 24- and 48-hour treatments. Lycopene, therefore, deserves further study as a potential chemopreventive/chemotherapeutic agent.     

The use of fetal bovine serum as delivery vehicle to improve the uptake and stability of lycopene in cell culture studies

Tetrahydrofuran (THF) has commonly been used to deliver carotenoids to cells but the use of THF is associated with cytotoxicity and low uptake efficiency of carotenoids. Here, we used fetal bovine serum (FBS) as the delivery vehicle for lycopene in comparison with THF, THF containing 0.0025 % butylated hydroxytoluene (THF/BHT), methyl-beta-cyclodextrin (M-beta-CD) and micelles in two human prostate cancer cell lines, DU145 and PC-3. Lycopene (10 mM) solubilized in THF/BHT and then diluted in FBS at ratios of 5 and 10 gave the highest lycopene uptake in DU145 cells. Using a dilution factor of 10, we found that lycopene (10 microm) carried in FBS in a cell-free system led to significantly less loss of lycopene than in THF, THF/BHT and M-beta-CD within 24 h of incubation. Lycopene solubilized in micelles was more stable than that in FBS within 24 h, but the micelle itself led to marked cytotoxicity to DU145 cells. Lycopene at 10 microm in FBS led to significantly higher uptake of lycopene in both cell lines than that in THF, THF/BHT or M-beta-CD within 24 h of incubation. When FBS was replaced with lipoprotein-deficient serum, the uptake of lycopene by DU145 cells was markedly decreased and was not significantly different from that of THF or THF/BHT. These results demonstrate that FBS is superior to THF, THF/BHT, M-beta-CD and micelles as a delivery vehicle for lycopene in prostate cell lines and that the lipoprotein of FBS is likely responsible for the improved stability and cellular uptake of lycopene.     

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.     

Lycopene and apo-12'-lycopenal reduce cell proliferation and alter cell cycle progression in human prostate cancer cells

Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8'-lycopenal, or apo-12'-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12'-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12'-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression.     

Wine Antioxidant Polyphenols Inhibit the Proliferation of Human Prostate Cancer Cell Lines

The effect of different wine antioxidant polyphenols (catechin, epicatechin, quercetin, and resveratrol) on the growth of three prostate cancer cell lines (LNCaP, PC3, and DU145) was investigated. A dose- and time-dependent inhibition of cell growth by polyphenols was found at nanomolar concentrations. The proliferation of LNCaP and PC3 cells was preferentially inhibited by flavonoids (catechin, epicatechin, and quercetin), whereas resveratrol was the most potent inhibitor of DU145 cell growth. Possible mechanisms of action were investigated: 1) The competition of polyphenols for androgen binding in LNCaP cells revealed significant interaction only in the case of high concentrations of quercetin, at least at five orders of magnitude higher than the concentrations needed for cell growth inhibition. All other phenols showed low interactions. 2) Oxygen species production after mitogen stimulation and H²O²2 sensitivity of these cell lines did not correlate with the observed antiproliferative effects, ruling out such a mode of action. 3) NO production revealed two different patterns: LNCaP and DU145 cells produced high concentrations of NO, whereas PC3 cells produced low concentrations. Phorbol ester stimulation of cells did not reveal any additional effect in LNCaP and DU145 cells, whereas it enhanced the secretion of NO in PC3 cells. Polyphenols decreased NO secretion. This effect correlates with their antiproliferative action and the inhibition of inducible NO synthase. It is therefore proposed that the antiproliferative effect of polyphenols is mediated through the modulation of NO production. In conclusion, our data show a direct inhibitory effect of low concentrations of antioxidant wine phenols on the proliferation of human prostate cancer cell lines mediated by the production of NO, further suggesting potential beneficial effects of wine and other phenol-containing foods or drinks for the control of prostate cancer cell growth.     

Influence of Lycopene on Cell Viability,Cell Cycle,and Apoptosis of Human Prostate Cancer and Benign Hyperplastic Cells

Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related mortality in men of the Western world. Lycopene has received attention because of its expcted potential to prevent cancer. In the present study, we evaluated the influence of lycopene on cell viability, cell cycle, and apoptosis of human prostate cancer cells and benign prostate hyperplastic cells. Using MTT assay, we observed a decrease of cell viability in all cancer cell lines after treatment with lycopene, which decreased the percentage of cells in G0/G1 phase and increased in S and G2/M phases after 96 h of treatment in metastatic prostate cancer cell lineages. Flow citometry analysis of cell cycle revealed lycopene promoted cell cycle arrest in G0/G1 phase after 48 and 96 h of treatment in a primary cancer cell line. Using real time PCR assay, lycopene also induced apoptosis in prostate cancer cells with altered gene expression of Bax and Bcl-2. No effect was observed in benign prostate hyperplasia cells. These results suggest an effect of lycopene on activity of human prostate cancer cells.     

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.