tannins and Prostatic-Neoplasms

Prostate cancer (PCa) cells exploit the aberrant lipid signaling and metabolism as their survival advantage. Also, intracellular storage lipids act as fuel for the PCa proliferation. However, few studies were available that addressed the topic of targeting lipid metabolism in PCa. Here, we assessed the tannic acid (TA) lipid-targeting ability and its capability to induce endoplasmic reticulum (ER) stress by reactive oxygen species (ROS) in PCa cells. TA exhibited dual effects by inhibiting lipogenic signaling and suppression of lipid metabolic pathways. The expression of proteins responsible for lipogenesis was down regulated. The membrane permeability and functionality of PCa were severely affected and caused nuclear disorganization during drug exposure. Finally, these consolidated events shifted the cell's survival balance towards apoptosis. These results suggest that TA distinctly interferes with the lipid signaling and metabolism of PCa cells.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Endoplasmic Reticulum Stress; Humans; Lipid Metabolism; Male; Prostate; Prostatic Neoplasms; Reactive Oxygen Species; Signal Transduction; Tannins

The aim of this study was to investigate the effects of plant phenolic compound tannic acid (TA) on proliferative, metastatic, invasive properties of prostate cancer (PCa) cells; PC-3 and LNCaP, as well as drug metabolizing and antioxidant enzymes. Characterization of TA was done by using FT-IR and NMR. TA dose dependently inhibited the proliferation of PC-3 and LNCaP cells with IC50 values 35.3 μM and 29.1 μM, respectively. Wound healing assay showed that TA significantly inhibited (92.7%) migration of PCa cells (p<0.0001). In addition, TA was found to have anti-invasive potential on PC-3 cells and it inhibited (80.9%, p<0.0001) invasion of PC-3 cells into matrigel. Only 17.8% of PC-3 cells can form colony in the 0.7% agarose after treatment of cells with TA at the IC50 value concentration. Furthermore, flow cytometry analyses with Annexin V-APC and 7-AAD staining demonstrated that TA increases early apoptosis rate of PC-3 cells by 25.8% and LNCaP cells by 20.9%. Besides, Western blot and qRT-PCR analyses also demonstrated that TA regulates protein and mRNA expressions of CYP17A1, CYP3A4, CYP2B6, NQO1, GSTM1 and GSTP1 enzymes. The results obtained from this study show that TA might be a good candidate for combinational therapy and highly effective strategic molecule for reducing the occurrence of PCa.

Topics: Cell Proliferation; Humans; Male; Neoplasm Invasiveness; Neoplasm Metastasis; Prostatic Neoplasms; Tannins

Several studies have documented the anticancer and chemopreventive efficacy of grape seed extract (GSE) against various malignancies including prostate cancer (PCA). GSE is a complex mixture of polyphenols including gallic acid (GA), catechin (Cat), epicatechin (Epi) and procyanidins-oligomers of Cat and Epi, some of which are esterified with GA. Initial studies to identify the GSE components cytotoxic to human prostate carcinoma (DU145) cells demonstrated that GA and several crude chromatographic fractions containing procyanidin dimers and trimers were biologically active. The focus of the present work was to purify 14 procyanidins from the fractions and to identify those with highest activity toward growth inhibition, cell death and apoptosis in DU145 cells. The most active procyanidin was identified by mass spectrometry and enzymatic hydrolysis as the 3,3'-di-O-gallate ester of procyanidin dimer B2 (Epi-Epi). B2-digallate exhibited dose-dependent effects on DU145 cells over the range 25-100 microM, whereas GA exhibited comparable activity at lower doses but was highly lethal at 100 microM. Structure-activity studies demonstrated that all three hydroxyl groups of GA are necessary for activity, but a free carboxylic acid group is not required even though esterification reduced the activity of GA. These data, and the fact that non-esterified B2 exhibited little or no activity, suggest that the galloyl groups of B2-digallate are primarily responsible for its effects on DU145 cells. Taken together, these data identify procyanidin B2-3,3'-di-O-gallate as a novel biologically active agent in GSE that should be studied in greater detail to determine its effects against PCA.

Topics: Anthocyanins; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dimerization; Humans; Male; Plant Extracts; Prostatic Neoplasms; Seeds; Spectrometry, Mass, Electrospray Ionization; Tannins; Vitis

Antioxidants are entities that play a vital role in protecting cells from free radical damage, which is implicated in cancer development. A detailed literature review on nutritional supplementation and cancer has demonstrated that antioxidants may be beneficial in preventing prostate cancer development. A reduced incidence of prostate cancer has been associated with high consumptions of antioxidants. The goal of this study was to utilize the ceramic drug delivery system to evaluate the behavior and response of LNCaP prostate cells upon treatment with epigallocatechin-3-gallate (EGCG), thymoquinone (TQ), and tannic acid (TA). After treatment with the various antioxidants, the groups were evaluated after 24, 48, and 72 hours of incubation. After all phases of incubation, groups treated with EGCG +TCP demonstrated the greatest reduction in cell count as well as the most cell membrane damage according to malondialdehyde (MDA) levels. In comparison to the control group, all groups demonstrated reductions in cell growth and decreased PSA levels that were significant according to one way analysis of variance (P < 0.001). Findings from this study revealed that sustained delivery with antioxidants may be a means of treating prostate cancer both safely as well as effectively. Future studies are needed to test the mechanisms behind these reactions.

Topics: Anticarcinogenic Agents; Antioxidants; Benzoquinones; Catechin; Cell Line, Tumor; Cell Proliferation; Cell Survival; Ceramics; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Humans; Male; Neoplasm Proteins; Prostatic Neoplasms; Tannins

Antioxidants are substances that function to protect cells from damage caused by unstable free radicals, which are responsible for damage that may lead to cancer. (Blot et al., 1993). Several antioxidants have been discussed for use in prevention and treatment of prostate carcinoma. Epidemiological evidence has indicated that these antioxidants may reduce the risk of prostate cancer by underlying mechanisms that remain unclear. The LNCaP cell line was introduced by inoculation from a supraclavicular lymph node metastasis of human prostate cancer (Horoszewicz et al., 1983). The aim of this study was to use the androgen-dependent LNCaP human prostate cancer cell line as a cell model to evaluate the physiological effects to conventional treatments with both low (LD) and high doses (HD) of epigallocatechin-3-gallate (EGCG), thymoquinone (TQ), and tannic acid (TA). Following treatment, cells were incubated and the various groups were evaluated at 24, 48, and 72 hours. After 24, 48, and 72 hours of incubation, all treated cells caused a reduction in cell growth, but the TQHD treated group seemed to be the most potent. The TQHD group also demonstrated the greatest decrease in total protein levels in comparison to the control. According to one-way analysis of variance (ANOVA), significant differences were observed (P < 0.001). Upon observation of the prostatic specific antigen (PSA) values, all groups showed decreased levels; however, the TQHD treated group showed an initial suppression after 24 hours and then finally adapted to treatment after 48 and 72 hours. Malondialdehyde (MDA) values were also assessed at the same three time periods (24, 48, and 72 hours) as an indicator of membrane integrity. After 24 hours of incubation, the TAHD group demonstrated the greatest increase in MDA levels. Morphologically, the cells demonstrated significant changes, such as swelling and irregularity in appearance upon antioxidant exposure. These findings reveal that antioxidants may serve as agents for prostate cancer prevention by providing safer and effective treatments for prostate cancer; however, further experiments are needed to understand the interactions involved.

Topics: Antineoplastic Agents; Antioxidants; Benzoquinones; Catechin; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Humans; Male; Prostatic Neoplasms; Tannins; Treatment Outcome

Geum quellyon Sweet, a perennial herb of the Rosaceae family, has been used in the traditional medicine of the Mapuche Amerindians of Chile to treat tooth neuralgia, gastric inflammation, prostatitis and to regulate menstruation, and for its diuretic and aphrodisiac properties. Although many benefits have been claimed for this plant, few scientific studies are available in the literature. In this study, we investigated the antioxidant activity of a methanolic extract of Geum quellyon roots. We also examined the anticancer action of this plant on Caco-2 (colon adenocarcinoma cells), DU-145 (androgen-insensitive prostate cancer cells) and KB (oral squamous carcinoma cells) human tumor cell lines. Our data showed that Geum quellyon extract, containing tannins, exhibits interesting antioxidant properties, expressed by its capacity to scavenge 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and superoxide anion (O(2)*-), to inhibit xanthine oxidase activity, to chelate metals, and to protect plasmid DNA from cleavage induced by hydroxyl radicals (*OH) and nitric oxide (NO). These results may explain, at least in part, its use in Mapuche traditional medicine for gastric inflammation and prostatitis. The assays on human tumor cell lines demonstrated that this natural product exhibits a inhibitory effect on all human cancer cells examined, and seem to indicate that necrosis cell death is triggered in KB cells and Caco-2, while apoptotic cell demise appears to be induced in DU-145. The effect evidenced in Caco-2 cells can be in part correlated to a modulation of redox-sensitive mechanisms.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Caco-2 Cells; Cell Line, Tumor; Chelating Agents; Chile; Comet Assay; DNA, Neoplasm; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Free Radical Scavengers; Geum; Humans; Hydrazines; Hydrogen Peroxide; KB Cells; L-Lactate Dehydrogenase; Male; Medicine, Traditional; Picrates; Plant Extracts; Plant Roots; Prostatic Neoplasms; Reactive Oxygen Species; Tannins; Tetrazolium Salts; Thiazoles; Ultraviolet Rays; Xanthine Oxidase

Tumor angiogenesis is a critical step for the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. From the screening of medicinal plants, we have identified 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) from the roots of Paeonia lactiflora that inhibited the binding of VEGF to KDR/Flk-1. PGG efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation and the growth of immortalized human microvascular endothelial cells, but did not affect the growth of HT1080 human fibrosarcoma and DU-145 human prostate carcinoma cells. PGG also blocked VEGF-induced capillary-like tube formation of endothelial cell on Matrigel. Our results suggest that PGG could be a candidate for developing anti-angiogenic agent.

Topics: Cell Division; Cell Movement; Collagen; Drug Combinations; Endothelium, Vascular; Fibrosarcoma; Humans; Hydrolyzable Tannins; Laminin; Male; Paeonia; Plant Extracts; Prostatic Neoplasms; Protein Binding; Proteoglycans; Receptors, Vascular Endothelial Growth Factor; Sodium-Potassium-Exchanging ATPase; Tannins; Umbilical Veins; Vascular Endothelial Growth Factor A

Topics: Absorption; Acid Phosphatase; Animals; Antibody Formation; Antigens; Dogs; Erythrocytes; Haplorhini; Hemagglutination Inhibition Tests; Hemagglutination Tests; Humans; Immunodiffusion; Immunoelectrophoresis; Male; Organ Specificity; Prostate; Prostatic Neoplasms; Rabbits; Species Specificity; Tannins; Tissue Extracts