Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-epileptic drug valproic acid is also under trial as an anti-cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti-neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA-derivatives (ACS2, ACS33) on pre-clinical prostate cancer models. PC3 and DU-145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up-regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU-145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti-tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer.
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PMID:New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma. 1826 64

Peroxisome proliferator-activated receptor-gamma (PPAR)-gamma is a ligand-activated transcriptional factor belonging to steroid receptor superfamily. PPAR-gamma plays a role in both adipocyte differentiation and tumorigenesis. Up to date, PPAR-gamma is expressed in various cancer tissues, and PPAR-gamma ligand induces growth arrest of these cancer cells. In this study, we examined the expression of PPAR-gamma in prostate cancer (PC) and testicular cancer (TC) by RT-PCR and immunohistochemistry, and we also examined the effect of PPAR-gamma ligand in these cells by MTT assay, hoechest staining, and flow cytometry. PPAR-gamma expression was significantly more extensive and intense in malignant tissues than in normal tissues. PPAR-gamma ligand induced the reduction of malignant cell viability through apoptosis. These results demonstrated that the generated PPAR-gamma in PC and TC cells might play an important role in the tumorigenesis. PPAR-gamma may become a new target in the treatment of PC and TC.
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PMID:Peroxisome Proliferator-Activated Receptor-gamma Is a Potent Target for Prevention and Treatment in Human Prostate and Testicular Cancer. 1831 13

Prostate cancer (PCa) is the most frequently diagnosed noncutaneous cancer and the leading cause of cancer related deaths in men in the United States and many other Asian countries. Dietary factors are considered as a strategic agent to control the risk of PCa. Lupeol, a triterpene, present in fruits and medicinal plants, has been shown to possess many pharmacological properties including anticancer effects. Here, effect of lupeol on cell proliferation and cell death was evaluated using human PCa cells, PC-3. In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner. Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded, which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene. The role of caspase-induced apoptosis was confirmed by increase in reactive oxygen species, loss of mitochondrial membrane potential followed by DNA fragmentation. Thus, our study suggests that lupeol possess novel antiproliferative and apoptotic potential against PCa.
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PMID:Regulation of signaling pathways involved in lupeol induced inhibition of proliferation and induction of apoptosis in human prostate cancer cells. 3235 7

We have initiated studies to enhance targeted delivery of an anticancer agent, curcumin, for prostate cancer treatment by incorporating this agent into the liposomes (nanodelivery vehicles primarily composed of phospholipids) coated with prostate membrane specific antigen specific antibodies. We prepared curcumin-loaded liposomes of various lipid compositions by sonication at an average size of 100-150 nm. Un-entrapped curcumin was removed by size exclusion chromatography. Data show that curcumin preferentially partitioned into liposomes prepared from dimyristoyl phosphatidyl choline (DMPC) and cholesterol among the various compositions tested. The anti-proliferative activity of liposomal curcumin was studied using two human prostate cancer cell lines (LNCaP and C4-2B) by a tetrazolium dye-based (MTT) assay. Treatment of cells with liposomal curcumin (5-10 microM) for 24-48 h at 37 degrees C resulted in at least 70-80% inhibition of cellular proliferation without affecting their viability. On the other hand, free curcumin exhibited similar inhibition only at 10-fold higher doses (>50 microM). We also observed that LNCaP cells were relatively more sensitive to liposomal curcumin mediated block of cellular proliferation than C4-2B cells. We are currently developing liposome formulations with targeting ability to further improve the efficacy of curcumin in vivo.
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PMID:Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells. 1842 40

Prostate cancer (PCA) is the most common cancer diagnosed in men and the second most common cause of death due to cancers after lung cancer. Metastasis of cancer cells involves multiple processes and various cytophysiological changes, including changed adhesion capability between cells and extracellular matrix (ECM) and damaged intercellular interaction. Silibinin, a naturally occurring flavonoid antioxidant found in the milk thistle, has recently been shown to have potent antiproliferative effect against various malignant cell lines. In the present study, PC-3 cells were incubated with various concentrations of silibinin for different times; then, cell cytotoxicity, cell adhesion and cell motility were assessed using MTT assay, cell-matrix adhesion assay and cell migration assay, respectively. The results showed that silibinin exerted a dose- and time-dependent inhibitory effect on the viability, motility and adhesion of highly metastatic PC-3 cells. These observations indicate that silibinin can probably inhibit metastasis in PCA.
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PMID:Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line. 1853 89

A series of novel substituted 1,2,3-benzotriazines based on the structures of vatalanib succinate (PTK787) and vandetanib (ZD6474) were designed and synthesized. The antiproliferative effects of these compounds were tested on microvascular endothelial cells (MVECs) using the MTT assay. Introduction of a methoxy and a 3-chloropropoxy group into the 1,2,3-benzotriazines increased the antiproliferative effects. 4-(3-Chloro-4- fluoroanilino)-7-(3-chloropropoxy)-6-methoxy-1,2,3-benzotriazine (8m) was the most effective compound. It was 4-10 fold more potent than PTK787 in inhibiting the growth of T47D breast cancer cells, DU145 and PC-3 prostate cancer cells, LL/2 murine Lewis lung cancer cells and B16F0 melanoma cells.
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PMID:Design, synthesis, and antitumor activities of some novel substituted 1,2,3-benzotriazines. 1859 67

Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agent. Recent studies have reported that ARBs have the potential to inhibit the growth of prostate cancer (PC) cells. Moreover, it was recently reported that Telmisartan (a kind of ARB) has peroxisome proliferator-activated receptor (PPAR)-gamma activation. We previously reported that PPAR-gamma ligand induces growth arrest of PC cells through apoptosis. In this study, we evaluated the effects of the Telmisartan and other ARBs on cell proliferation in several PC cell lines. We used normal prostate stromal cell (NPC), human hormone-refractory PC (PC3), androgen-independent PC (DU-145) and androgen-dependent PC (LNCaP) cell lines. Effects of Telmisartan and other ARBs (Candesartan, Valsartan, Irbesartan and Losartan) on PC cell growth were examined by MTT assay. Flow cytometry and Hoechst staining were used to determine whether or not ARBs induce apoptosis. Telmisartan caused marked inhibition of PC cells in concentration-dependent and time-dependent manner. PC cells with treatment of 100 microM Telmisartan induced early apoptosis and DNA fragmentation. However, NPC with treatment of 100 microM Telmisartan did not induce apoptosis or DNA fragmentation. Furthermore, other ARBs had no effect on cell proliferation in the PC cells and NPC. Telmisartan may mediate potent antiproliferative effects against PC cells through PPAR-gamma. Thus, Telmisartan is a potent target for prevention and treatment in PC.
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PMID:Telmisartan is a potent target for prevention and treatment in human prostate cancer. 1863 89

Sonicated arsonoliposomes were prepared using arsonolipid with palmitic acid acyl chain (C16), mixed with phosphatidylcholine (PC)-based or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based, and cholesterol (Chol) with C16/DSPC/Chol 8:12:10 molar ratio. PEG-lipid (1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated to polyethylenoglycol 2000) containing vesicles (PEGylated-arsonoliposomes; PC-based and DSPC-based) were also prepared. The cytotoxicity of these arsonoliposomes towards different cancer cells (human promyelocytic leukaemia NB4, Prostatic cancer PC3, human breast adenocarcinoma MDA-MB-468, human T-lymphocyte (MT-4) and also towards human umbilical vein endothelial cells (HUVECs) was evaluated by calculating the arsonoliposome-induced growth inhibition of the cells by the MTT assay. IC-50 values were interpolated from cell number/arsonoliposome concentration curves. The results reveal that all types of arsonoliposomes evaluated significantly inhibit the growth of most of the cancer cells studied (PC3, NB4, MT4) with the exception of the MDA-MB-468 breast cancer cells which were minimally affected by arsonoliposomes; in some cases even less than HUVEC. Nevertheless, for the same cell type the differences between the different types of arsonoliposomes were significant but not proportional to their stability, indicating that the formation of arsonoliposomes with very stable membranes is not a problem for their anticancer activity. Thereby it is concluded that arsonoliposome composition should be adjusted in accordance to their in vivo kinetics and the desired, for each specific application, biodistribution of As and/or encapsulated drug.
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PMID:Does the lipid membrane composition of arsonoliposomes affect their anticancer activity? A cell culture study. 1872 12

The present study examined the anti-proliferative effects of piplartine on the human prostate cancer cell line PC-3. This is the first report demonstrating the piplartine anti-cancer activity toward prostate cancer cell lines, although its precise mechanism of action is still not completely defined. In MTT assays, it preferentially inhibited growth of androgen-independent PC-3 cells in a dose-dependent (3-30 microM) and time-dependent (12-48 h) manner. In PC-3 cells, it showed an IC50 of 15 microM after 24 h of treatment. After a 24-30 microM treatment for 24 h, there were some reduction of cell volume, cell vacuolization, chromatin condensation and increased number of apoptotic cells visible by light and fluorescence microscopy. Agarose gel electrophoresis revealed that cells treated with piplartine exhibited DNA fragmentation. In addition, growth inhibition of PC-3 cells was associated with G2/M arrest and sub-G1 accumulation. Higher concentrations (24-30 microM) of piplartine modulated apoptosis-related protein expression by down-regulating cdc-2 expression and up-regulating PARP/procaspase-3 cleavage. Also, PC-3 cells treated with piplartine demonstrated caspase-3 activation, as observed with an in vitro caspase-3 colorimetric assay kit. Taken together, these results demonstrated that high concentrations of piplartine exhibited anti-proliferative and anti-cancer effects on PC-3 cells and that caspase-3-mediated PARP cleavage and cell cycle arrest at G2/M phase are involved in the underlying cellular mechanism of the apoptosis process.
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PMID:Piplartine induces caspase-mediated apoptosis in PC-3 human prostate cancer cells. 1881 19

Taxanes are chemotherapeutic agents commonly used to treat various carcinomas. Dietary antioxidants, such as vitamin E, green tea extracts, and isoflavones have been used against prostate cancer, and exhibit anticancer effects both in vitro and in vivo. We evaluated the combined effect of taxol (paclitaxel) with pyrrolidine dithiocarbamate, vitamin E, epigallocatechin gallate, and genistein in killing hormone-refractory prostate cancer cells. Those agents were tested on the hormone-refractory prostate cancer cell line PC-3, and the viability of the cells was determined using MTT {3 (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium} assay after drug treatment. PC-3 cells were sensitive to these drugs with 50% inhibitory concentrations of 0.1, 23, 220, 1122, and 260 microM, for taxol, pyrrolidine dithiocarbamate, epigallocatechin gallate, genistein, and vitamin E, respectively. Genistein, pyrrolidine dithiocarbamate, and epigallocatechin gallate showed synergistic cytotoxicity to PC-3 cells when combined with 0.01 microM taxol. Only high concentration of vitamin E showed a synergistic effect with this dose of taxol. Further study revealed that 3 combinations could induce sub-G1 phase of cell cycle, induce apoptosis, and increase caspase activity and decrease Bcl-2 expression simultaneously. In conclusion, in addition to vitamin E, incorporation of these antioxidants with taxan-based cytotoxic therapies offers encouraging strategies for combating hormone-refractory prostate cancers.
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PMID:Taxol synergizes with antioxidants in inhibiting hormal refractory prostate cancer cell growth. 1881 8


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