Hormone-independent Prostate Cancer Cell Research Articles

Anticancer Effects of Propolis Extracts Obtained with the Cold Separation Method on PC-3 and DU-145 Prostate Cancer Cell Lines

Plant extracts are increasingly tested for their biological activity and interactions with neoplastic cells. One of such sources of biologically active substances is propolis. This product has been known for thousands of years and is widely used in alternative, folk medicine. Articles describing its effects on the metabolism and cell signaling pathways of neoplastic cells derived from different organs are also published more and more frequently. The purpose of our study was to evaluate the biological activity of propolis extract produced with the cold separation method into hormone-dependent and hormone-independent prostate cancer cell lines. In our study, the propolis extracts showed at least an inhibitory effect on the growth of PC-3 and DU-145 neoplastic cells. Our results suggest that propolis extracts obtained with the cold separation method may be considered as promising compounds for the production of health-promoting supplements.

Vaccinium myrtillus L. extract and its native polyphenol-recombined mixture have anti-proliferative and pro-apoptotic effects on human prostate cancer cell lines.

Vaccinium myrtillus berry extract (VME) and a recombined standard mixture (RSM) of its main native phenolic compounds were investigated for cell growth inhibition and pro-apoptotic activity on hormone-dependent (LNCaP) and hormone-independent (PC3 and DU-145) prostate cancer (PCa) cell lines. Normal prostate epithelial cells (PrEC) were also studied in comparison. VME hindered anchorage-dependent PCa cell proliferation in a dose-dependent manner, that is, at 1/800 (v/v) dilution for LNCaP and PC3, and 1/100 (v/v) dilution for DU-145 (corresponding to 14.15 and 113.2 μg cyanidin-3-O-glucoside equivalents per ml of culture medium), respectively. VME had a growth inhibitory effect towards PrEC at the same dilution of DU-145 cells although the IC50 values indicated that PrEC are more resistant than PCa cell lines. VME also reduced the anchorage-independent growth of PCa cells. The study of the apoptotic profile (i.e., non-apoptotic, early apoptotic, late apoptotic and necrotic cells) evidenced that the apoptotic rate (early+late) was statistically higher in all three cell lines exposed to VME compared to control. Anchorage-dependent and anchorage-independent growth inhibition of RSM was very similar to that displayed by VME. Moreover, RSM exerted its growth inhibitory effect also under hypoxia, the latter representing a biological condition known to sustain PCa proliferation and aggressiveness.

Differential expression of microRNA-218 in hormone-dependent and hormone-independent prostate cancer cell lines

Objective To verify and analyze the expression of microRNA-218 in hormone-dependent and hormone-independent prostate cancer cell lines. Methods Specific SYBR Green quantitative real-time polymerase chain reaction(RT-PCR) was used to detect the relative expression of microRNA-218 in hormone-dependent prostate cancer LNCaP cell line and hormone-independent prostate cancer C4-2, PC-3 and DU-145 cell lines, and the differences were verified and analyzed. Results The expression of MicroRNA-218 was not different in C4-type, PC-3 and DU-145 three hormone-independent prostate cancer cell lines(P>0.05), but was significantly higher than that in hormone-dependent prostate cancer cell line LNCaP(P<0.05). Conclusions MicroRNA-218 is involved in the progression from steroid-dependent to hormone-independent prostate cancer and is expected to become a biomarker for predicting the progression of prostate cancer. Key words: Prostatic Neoplasms; Cell Line; MicroRNAs

Effect of polyunsaturated fatty acids on proliferation and survival of prostate cancer cells.

Progression of prostate cancer to lethal forms is marked by emergence of hormone-independent proliferation of the cancer cells. Nutritional and epidemiological studies have indicated that prostate cancer progression is correlated with the consumption of polyunsaturated fatty acids (PUFA). To shed additional light on the cell-level mechanisms of the observed correlation, we compared the sensitivity of hormone-dependent and hormone-independent prostate cancer cells to growth medium supplementation with free PUFAs in a cell proliferation and viability assay. Our data show that the hormone-dependent cells are comparatively insensitive to various PUFAs, at the same time as the growth and viability of hormone-independent cells lines are strongly inhibited by most of the tested PUFAs, whether n–3 or n–6. We speculate that this difference may be at least partially responsible for the observed effects of specific dietary lipids in prostate cancer. The new data strengthen the case for dietary intervention as part of potential new therapeutic strategies seeking to impede prostate cancer progression.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure.

Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells.

Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. Maspin can enhance the sensitivity of HRPC cells to curcumin treatment.

HMGB1-mediated autophagy confers resistance to gemcitabine in hormone-independent prostate cancer cells.

As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines. The results demonstrated that the autophagy markers were induced significantly in HIPC cells subsequent to gemcitabine treatment. Meanwhile, administration of gemcitabine to HIPC cells increased the expression of high mobility group box1 (HMGB1). Furthermore, the gemcitabine-induced autophagy response was attenuated in stable HIPC cells harboring HMGB1 shRNA. Notably, the HIPC cells stably transfected with HMGB1 shRNA or treated with autophagy inhibitors were more sensitive to gemcitabine compared with the control group. These data suggested that inhibition of HMGB1 increased the sensitivity to gemcitabine by decreasing autophagy response in HIPC cells. Overall, the present findings demonstrate a new mechanism for the resistance to gemcitabine in HIPC cell lines.

Carnosol inhibits Hedgehog signaling pathway in both LNCaP and DU145 prostate cancer cell lines

To investigate the effect of carnosol on the Hedgehog (HH) signaling pathway in human hormone-dependent prostate cancer cell line LNCaP and hormone-independent prostate cancer cell line DU145. The expression levels of glioma-associated oncogene homolog 1 (Gli1) and Sonic hedgehog (Shh) in human prostate cancer tissues were detected by immunohistochemistry. After treated with carnosol (0.25-16 μmol/L), the cell survival of LNCaP and DU145 cells were detected by MTT assay. The expression levels of Gli1 and Shh mRNA and protein in the two cells were detected by qRT-PCR and western blot, respectively. The apoptosis was determined by the caspase-3 activity assay. Results showed that Shh and Gli1 were upregulated in cancer tissues. The inhibitory effect of carnosol on cell survival was enhanced with concentration, suggesting both LNCaP and DU145 cells were sensitive to carnosol. The inhibitory effects of carnosol on Gli1 and Shh mRNAs in the hormone-dependent LNCaP prostate cancer cell was stronger than that in the hormone-independent DU145 prostate cancer cells. Carnosol downregulated the expression of Gli1 in nucleus, and Shh in cells. Greater carnosol concentration resulted in lower levels of Gli1 and Shh. Carnosol increased caspase-3 activity in a dose-dependent manner, suggesting that carnosol promotes cell apoptosis. Thus, carnosol can inhibit the proliferation and induce the apoptosis of prostate cancer cells in vitro, and its mechanism might be associated with the inhibiting of HH signaling pathway. Although the inhibitory effect of carnosol on hormone-dependent LNCaP prostate cancer cells is stronger than hormone-independent DU145 prostate cancer cells, carnosol might be a potential drug for hormone-independent prostate cancer.

New gonadotropin-releasing hormone glycolipids with direct antiproliferative activity and gonadotropin-releasing potency

Gonadotropin-releasing hormone (GnRH) is an endogenous peptide with a short biological half-life. Although GnRH analogs (eg. triptorelin) are developed with enhanced stability compared to the native peptide, they still suffer from poor biological stability and pharmacokinetic properties. Furthermore, they are only effective in the treatment of hormone-dependent reproductive cancers. In this study we applied lipidation and glycosylation along with D-amino acid substitution at position 6 (D-Trp 6 ) to improve the stability, permeability, and consequently the potency of the GnRH peptide and triptorelin. We showed that the conjugation of GnRH with a lipid moiety and carbohydrates made all modified constructs ( 1– 8 ) more stable than the parent peptide against enzymatic degradation (5.5–6.5 times). Two of the lactose-modified glycolipopeptides, 3 and 6 , showed 27 and 16 times higher membrane permeability than the parent GnRH, respectively. All analogs with D-Trp 6 -substitution ( 4–6 ) exerted GnRH receptor-mediated antiproliferative activity in prostate and ovarian GnRH-receptor positive cell lines. They were more potent than triptorelin in the hormone-independent prostate cancer cell line: DU145. Compound 6 (lactose-modified) was the most potent analog for stimulating the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) gonadotropins from rat pituitary cells in vitro . The same glycolipopeptide exhibited a higher efficacy and duration of action in stimulating the release of LH than triptorelin in a preclinical mouse model. The superior activity of lipid- and carbohydrate-substituted triptorelin analog 6 made it a promising candidate for the development of new GnRH agonists to treat both hormone-dependent and hormone-refractory prostate cancer.

Oridonin induces G2/M cell cycle arrest and apoptosis via the PI3K/Akt signaling pathway in hormone-independent prostate cancer cells.

Oridonin is an active constituent isolated from the traditional Chinese herb Rabdosia rubescens, which exerts antitumor effects in experimental and clinical settings. However, its antitumor effects and underlying mechanisms on prostate cancer cells have not yet been clearly identified. In the present study, the androgen-independent prostate cancer PC3 and DU145 cell lines were used as models to investigate the effects and possible mechanisms of oridonin on cellular proliferation and apoptosis. Results demonstrated that oridonin inhibited cellular proliferation, and was able to significantly induce G2/M cell cycle arrest and apoptosis. Detailed signaling pathway analysis by western blotting demonstrated that the expression levels of p53 and p21 were upregulated, whereas the expression of cyclin-dependent kinase 1 was downregulated following oridonin treatment, which led to cell cycle arrest in the G2/M phase. Oridonin also upregulated the proteolytic cleaved forms of caspase-3, caspase-9 and poly (ADP-ribose) polymerase. Furthermore, the protein expression levels of B-cell lymphoma 2 were decreased and those of Bcl-2-associated X protein were increased following oridonin treatment. In addition, oridonin treatment significantly inhibited the expression of phosphoiniositide-3 kinase (PI3K) p85 subunit and the phosphorylation of Akt. The downstream gene murine double minute 2 was also downregulated, which may contribute to the elevated expression of p53 following oridonin treatment. In conclusion, the results of the present study suggested that oridonin is able to inactivate the PI3K/Akt pathway and activate p53 pathways in prostate cancer cells, resulting in the suppression of proliferation and the induction of caspase-mediated apoptosis.

Abstract B16: Combination of docetaxel with histone deacetylase inhibitor inhibits AR signaling synergistically in hormone-independent 22Rv1 prostate cancer cells

Abstract Globally prostate cancer is the sixth leading cause of cancer-related death in men, and it is now the first in the United Kingdom and second in the United States. At the early stage, prostate cancer growth and progression depend on androgen receptor (AR) signaling. Therefore, androgen-deprivation therapy (ADT) is effective to patient with prostate cancer by inhibition of androgen synthesis. With time, however, most patients with prostate cancer eventually lose sensitivity to androgen withdrawal and progress to the development of castration-resistant prostate cancer (CRPC). Though docetaxel is a standard of care therapy in CRPC, most of patients develop resistance to this therapy. Therefore, the novel therapeutic strategies and combination therapy are needed to overcome this resistance. In this study, we examined whether histone deacetylase inhibitor (HDACI), suberoylanilide hydroxamic acid (SAHA) might enhance the effect of docetaxel in CRPC. Hormone-independent 22Rv1 cells harboring AR were treated with docetaxel and/or SAHA. Co-treatment of docetaxel and SAHA inhibited the growth of 22Rv1 cells synergistically. Combination treatment decreased the levels of AR, prostate specific antigen (PSA), and anti-apoptotic Bcl-2 proteins (Mcl-1, Bcl-xl) more efficiently compared with docetaxel or SAHA alone, when it analyzed by Western blot. And combination treatment increased activation of caspase-3 remarkably, while docetaxel or SAHA alone increased it slightly. Moreover, immunocytochemistry and analysis of nuclear fractionated proteins showed that combination treatment induced acetylation and bundling of tubulin, inhibiting nuclear accumulation of AR significantly. These results suggested that docetaxel in combination with SAHA inhibited cell growth efficiently and induced apoptosis by repressing expression and translocation to nucleus of AR in 22Rv1 cells, and this combination can be a useful therapeutics for the treatment of CRPC patients. Citation Format: Ha-Gyeong Kim, Jung Jin Hwang, Choung-Soo Kim. Combination of docetaxel with histone deacetylase inhibitor inhibits AR signaling synergistically in hormone-independent 22Rv1 prostate cancer cells. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B16.

Thrombomodulin mediates the migratory ability of hormone-independent prostate cancer cells through the regulation of epithelial-to-mesenchymal transition biomarkers

Thrombomodulin (TM) is highly expressed in endothelial cells and plays the key role in maintaining physical homeostasis. In addition, many pieces of evidence also show that TM contains the diagnostic value for malignant diseases. TM has been found to correlate with metastatic status in multiple cancers, but its role in prostate cancer progression remains unclear. TM expression was determined in prostate cancer cells (DU-145 and PC-3 cells) using real-time PCR and Western blotting. TM expression was manipulated in prostate cancer cells using TM-specific shRNA and an overexpression system. The proliferation, adhesion, and migratory ability of prostate cancer cells expressing various TM levels were determined using the x'Celligence biosensor system and a transwell migration assay. Higher levels of TM transcription and translation were found in DU-145 cells and were negatively correlated with the low migratory ability of DU-145 cells. After silencing TM expression in DU-145 cells, cell growth decreased, but cell adhesion and migration dramatically increased. TM overexpression in PC-3 cells reduced their metastatic ability. We investigated the possible mechanisms of this phenomenon and determined that the enhanced cell migration was mediated through the expression of E-cadherin and vimentin. TM may be a modulator of hormone-independent prostate cancer (HIPC) metastasis. The downregulation of TM expression enhanced the migratory ability of these cells via an increase in vimentin expression and a decrease in E-cadherin expression.

Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs

A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4-dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using a recombinant PCA-1/ALKBH3, 1-(1H-5-methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H-pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral administration. As expected, continuously administering 35 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.

N‐substituted Piperazinopyridylsteroid Derivatives as Abiraterone Analogues Inhibit Growth and Induce Pro‐apoptosis in Human Hormone‐independent Prostate Cancer Cell Lines

Nine new 17-(piperazin-1-yl)pyridin-5-yl)steroids as abiraterone analogues were synthesized. Compounds 5d and 5g showed selective activities against 17α-hydroxylase/C17,20-lyase (CYP17A1) and aromatase (CYP19), respectively. IC50 values of 5d were 5.09 and >50 μm, whereas these values for 5g were >50 μm and 7.40 μm, respectively, for CYP17A1 and CYP19. Molecular modelling highlighted that the inhibitor designed to bind cytochrome P450 haem iron is a necessary condition but not the only rationale to explain inhibitory activity. These abiraterone analogues were then evaluated on hormone-independent prostate cancer cell lines DU-145 and PC-3 and on hormone-dependent breast and prostate cancer cell lines MCF-7 and LNCaP, respectively. Compounds 5e, 5g and 5i have showed potent activities only on hormone-independent prostate cancer cell lines DU-145 and PC-3 with 60-85% inhibition of both cell viability and growth at 10 nm with pro-apoptotic mechanism as illustrated in PC-3 cells by DNA ladder assay and Western blotting of Bax, Casp-3 and its substrate, the poly (ADP-ribose) polymerase. We conclude that hybrid heterocycle steroids could be good lead compounds in the drug design especially against hormone-independent prostate cancer.

Beyond the Limits of Oxygen: Effects of Hypoxia in a Hormone-Independent Prostate Cancer Cell Line

Prostate cancer (PCa) has a high incidence worldwide. One of the major causes of PCa resistance is intratumoral hypoxia. In solid tumors, hypoxia is strongly associated with malignant progression and resistance to therapy, which is an indicator of poor prognosis. The antiproliferative effect and induced death caused by doxorubicin, epirubicin, cisplatin, and flutamide in a hormone-independent PCa cell line will be evaluated. The hypoxia effect on drug resistance to these drugs, as well as cell proliferation and migration, will be also analyzed. All drugs induced an antiproliferative effect and also cell death in the cell line under study. Hypoxia made the cells more resistant to all drugs. Moreover, our results reveal that long time cell exposure to hypoxia decreases cellular proliferation and migration. Hypoxia can influence cellular resistance, proliferation, and migration. This study shows that hypoxia may be a key factor in the regulation of PCa.

Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer potential of VK2 in both androgen-dependent and -independent prostate cancer cells. Our investigations show that VK2 is able to suppress viability of androgen-dependent and androgen-independent prostate cancer cells via caspase-3 and -8 dependent apoptosis. We also show that VK2 treatment reduces androgen receptor expression and PSA secretion in androgen-dependent prostate cancer cells. Our results also implicate VK2 as a potential anti-inflammatory agent, as several inflammatory genes are downregulated in prostate cancer cells following treatment with VK2. Additionally, AKT and NF-kB levels in prostate cancer cells are reduced significantly when treated with VK2. These findings correlated with the results of the Boyden chamber and angiogenesis assay, as VK2 treatment reduced cell migration and angiogenesis potential of prostate cancer cells. Finally, in a nude mice model, VK2 administration resulted in significant inhibition of both androgen-dependent and androgen-independent tumor growth. Overall, our results suggest that VK2 may be a potential therapeutic agent in the treatment of prostate cancer.

N-substituted piperazinopyridylsteroid derivatives as abiraterone analogues inhibit growth and induce pro-apoptosis in human hormone-independent prostate cancer cell lines.

N-substituted piperazinopyridylsteroid derivatives as abiraterone analogues inhibit growth and induce pro-apoptosis in human hormone-independent prostate cancer cell lines.

Physangulidine A, a Withanolide from Physalis angulata, Perturbs the Cell Cycle and Induces Cell Death by Apoptosis in Prostate Cancer Cells

Recently, our group reported the discovery of three new withanolides, physangulidines A-C, from Physalis angulata. In this study, the biological effects of physangulidine A (1), which was the most active and abundant of the three new constituents, are described. It was found that 1 significantly reduces survival in clonogenic assays for two hormone-independent prostate cancer cell lines. Flow cytometry and confocal microscopy studies in DU145 human prostate cancer cells indicated that 1 induces cell cycle arrest in the G(2)/M phase and causes defective mitosis. It was determined also that 1 produces programed cell death by apoptosis, as evidenced by biochemical markers and distinct changes in cell morphology. These results imply that the antimitotic and proapoptotic effects of 1 may contribute significantly to the biological activities and potential medicinal properties of its plant of origin.

Anti-Tumor Effect of AlkB Homolog 3 Knockdown in Hormone- Independent Prostate Cancer Cells

Castrate resistant prostate cancer (CRPC) is a disease that is resistant to both hormone therapy and chemotherapy. At present, no curative therapy for CRPC has been established. Therefore, it is necessary to determine a novel molecular target for the development of therapeutic agents. We previously reported that AlkB homolog 3 (ALKBH3) is highly expressed in prostate cancer but not in benign prostatic hyperplasia or in normal prostate epithelium and that the expression levels of ALKBH3 protein are significantly correlated with the hormone-independent state of prostate cancer. Moreover, ALKBH3 regulates the invasion of prostate cancer cells via the regulation of matrix metalloproteinase 9. Here, we show that ALKBH3 gene silencing markedly induces apoptosis in hormone-independent prostate cancer cell line DU145 but not in the normal prostate epithelial cell line PNT2. Moreover, the in vivo tumorigenicity of DU145 cells was significantly inhibited by the administration of ALKBH3 siRNA. Furthermore, the anchorage-independent growth of DU145 cells was inhibited by ALKBH3 knockdown and promoted by ALKBH3 overexpression, significantly. ALKBH3 shRNA-expressing prostate cancer cells formed significantly smaller tumors than those of control shRNA transfectants in an in vivo xenograft model. These findings suggest that ALKBH3 is a promising target molecule for the development of CRPC therapeutic agents.

Abstract 1999: Specific pomegranate juice components are potential inhibitors of prostate cancer metastasis

Abstract Introduction: Prostate cancer is the second-leading cause of cancer-related mortality in U.S men. Early stages can be controlled with hormone ablation therapy that suppresses the rate of prostate cancer growth. However, over time, the cancer overcomes its hormone dependence, becomes highly aggressive and metastasizes to the lymph nodes and bone marrow. Recently, Pomegranate juice (PJ) has been identified as a natural product that inhibits prostate cancer progression. In an UCLA phase II clinical trial, patients with rising PSA were given 8 oz of PJ by mouth daily. PSA doubling time significantly increased with treatment from a mean of 15 months to 54 months post-treatment. We have shown previously that PJ inhibits the migratory and metastatic properties of prostate cancer cells by stimulating cell adhesion and inhibiting cell migration and chemotaxis. However, the soluble phase of PJ contains many components and as a whole it is difficult to determine how to best maximize its use in treating prostate cancer. A way to overcome this challenge is to identify chemical components of PJ responsible for the anti-metastatic effect of whole juice. Methods: By using two hormone-independent prostate cancer cell lines PC3 and DU145 and one hormone-sensitive cell line LNCaP, we took an integrative approach using Affymetrix gene arrays and miRNA PCR arrays to identify specific PJ components that have similar effects as the juice on cell adhesion, migration and chemotaxis. Results: We show that the specific PJ components luteolin, ellagic acid and punicic acid individually inhibit growth of hormone-dependent and -independent prostate cancer cells, and also inhibit their migration and their chemotaxis towards SDF1α, a factor that is important in prostate cancer metastasis to the bone. However, the greatest effects were observed when the three components were used together. In addition, our Affymetrix gene array results show that these components also increase the expression of cell adhesion genes and decrease expression of genes involved in cell cycle control and cell migration. Moreover, miRNA PCR array results show that these components increase several well-known tumor-suppressive miRNAs and decrease several oncogenic miRNAs. We also show that these components inhibit the CXCR4/SDF1α chemotaxis axis. Moreover, when taken together, the integrated results of the gene and miRNA arrays show a powerful correlation in regulation of function by the specific genes important in processes critical for metastasis. Conclusion: Our results suggest that these components may be a more effective inhibitor of prostate cancer metastasis than the whole juice. Chemical modification of these compounds could further enhance their bioavailability and efficacy of treatment. Moreover, because the mechanisms of metastasis are similar for most cancers, these PJ components may also be effective in treatment of metastasis of other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1999. doi:1538-7445.AM2012-1999