pectins and Prostatic-Neoplasms

This trial investigated the tolerability and effect of modified citrus pectin (Pecta-Sol) in 13 men with prostate cancer and biochemical prostate-specific antigen (PSA) failure after localized treatment, that is, radical prostatectomy, radiation, or cryosurgery. A total of 13 men were evaluated for tolerability and 10 for efficacy. Changes in the prostate-specific antigen doubling time (PSADT) of the 10 men were the primary end point in the study. We found that the PSADT increased (P-value<0.05) in seven (70%) of 10 men after taking MCP for 12 months compared to before taking MCP. This study suggests that MCP may lengthen the PSADT in men with recurrent prostate cancer.

Topics: Aged; Citrus; Humans; Male; Middle Aged; Pectins; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Radiotherapy is one of the primary therapies for localized prostatic carcinoma. Therefore, there is an emerging need to sensitize prostatic cancer cells to chemotherapy/radiotherapy. Modified citrus pectin (MCP) is an effective inhibitor of galectin-3 (Gal-3), which is correlated with tumor progression, proliferation, angiogenesis, and apoptosis.. This study was directed to evaluate the efficacy of combining ionizing radiation (IR) with MCP on PCa cells.. Effects of treatments on PCa cells survival were evaluated using XTT assay, flow cytometry, and clonogenic survival assay. Expression of selected proteins was estimated using western blotting. Cell motility, migration, and invasion were determined. Contribution of reactive oxygen species production to treatment effects on cell viability was tested.. Radiotherapy combined with MCP reduced viability and enhanced radiosensitivity associated with a decrease in Gal-3, cleavage of the precursor of caspase-3, increased expression of the pro-apoptotic protein Bax, and downregulation of DNA repair pathways, poly-ADP-ribose polymerase, and proliferating cell nuclear antigen. MCP significantly reduced the invasive and migratory potential of PCa cells. Combining sodium pyruvate with MCP and IR mitigated the effect on cell viability.. Our findings demonstrated that MCP sensitized PCa cells to IR by downregulating anti-apoptotic Gal-3, modulating DNA repair pathways, and increasing ROS production. For the first time the correlation between MCP, radiotherapy, and Gal-3 for prostatic cancer treatment was found. In addition, MCP reduced the metastatic properties of PCa cells. These findings provide MCP as a radiosensitizing agent to enhance IR cytotoxicity, overcome radioresistance, and reduce clinical IR dose.

Topics: Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; DNA Repair; Down-Regulation; Flow Cytometry; Galectin 3; Humans; Male; Neovascularization, Pathologic; PC-3 Cells; Pectins; Prostatic Neoplasms; Radiation Tolerance; Radiation-Sensitizing Agents; Reactive Oxygen Species

The objective of this study was to evaluate the combined effect of a known galectin-3 inhibitor, PectaSol-C modified citrus pectin (MCP), and 2 novel integrative polybotanical compounds for breast and prostate health, BreastDefend (BD) and ProstaCaid (PC), on invasive behavior in human breast and prostate cancer cells in vitro, respectively.. The effect of MCP and BD and of MCP and PC on invasiveness was assessed by cell adhesion, cell migration, and cell invasion assays. Secretion of urokinase plasminogen activator (uPA) was determined by Western blot analysis.. Although low concentrations of MCP (0.25-1.0 mg/mL) do not suppress cell adhesion of breast or prostate cancer cells, the combination of MCP with BD or PC synergistically inhibits adhesion of these cells. Dose-dependent inhibition of breast and prostate cancer cell migration by MCP (0.25-1.0 mg/mL) is synergistically enhanced by BD (20 µg/mL) and PC (10 µg/mL), respectively. BD or PC did not further inhibit the invasion of breast and prostate cancer cells by MCP; however, the combination of MCP with BD or PC suppressed secretion of uPA from breast and prostate cancer cells, respectively.. The combination of MCP with BD and of MCP with PC synergistically inhibits the metastatic phenotypes of human breast and prostate cancer cells, respectively. Further studies confirming these observations in animal models of breast and prostate cancer metastasis are warranted.

Topics: Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Citrus; Drug Synergism; Female; Galectin 3; Humans; Integrative Medicine; Male; Neoplasm Invasiveness; Pectins; Plant Extracts; Prostatic Neoplasms; Urokinase-Type Plasminogen Activator

The effect of PectaSol on Dox (Doxorubicin) cytotoxicity in terms of apoptosis and cell cycle changes in PCa (prostate cancer) cell lines (DU-145 and LNCaP) has been investigated. Combination of PectaSol and Dox resulted in a viability of 29.4 and 32.6% (P<0.001) in DU-145 and LNCaP cells. The IC₅₀ values decreased 1.5-fold and 1.3-fold in the DU-145 and LNCaP cells respectively. In the DU-145 cells, combination of PectaSol and Dox resulted in a reduction in p27 gene and protein expression (P<0.001). In LNCaP cells, this combination increased p53, p27 and Bcl-2 expression. Treatment with both drugs in DU-145 cells led to an increase in sub-G₁ arrest (54.6% compared with 12.2% in Dox). In LNCaP cells, combination of the drugs led to an increased in G₂/M arrest (61.7% compared with 53.6% in Dox). Based on these findings, progressive cytotoxicity effect of Dox and PectaSol together rapidly induce cell death in DU-145 through apoptosis and in LNCaP cells through cell cycle arrest (G₂/M arrest).

Topics: Antibiotics, Antineoplastic; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; Cyclin-Dependent Kinase Inhibitor p27; Doxorubicin; G2 Phase Cell Cycle Checkpoints; Humans; M Phase Cell Cycle Checkpoints; Male; Pectins; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53

To demonstrate the efficacy of PectaSol-C modified citrus pectin (MCP) on prostate cancer in vitro.. Cytotoxicity analysis of PectaSol-C was performed by MTT assay, as were parallel studies with the former brand version of MCP called PectaSol. Apoptosis and inhibition of cell growth were investigated by Western blotting.. Androgen-dependent and -independent human prostate cancer cell lines (LNCaP and PC3, respectively), androgen-dependent and -independent murine prostate cancer cell lines (CASP2.1 and CASP1.1, respectively), as well as noncancerous human benign prostate hyperplasia BPH-1 cell line, were used in the study. MTT assay revealed that 1.0% PectaSol exerted cytotoxicity on LNCaP, PC3, CASP2.1, CASP1.1, and BPH-1 cells for 4-day treatment by 48.0% +/- 2.1%, 54.4% +/- 0.3%, 15.4% +/- 0.8%, 46.1% +/- 1.7%, and 27.4% +/- 1.6%, respectively; whereas 1.0% PectaSol-C showed cytotoxity by 52.2% +/- 1.8%, 48.2% +/- 2.9%, 23.0% +/- 2.6%, 49.0% +/- 1.3%, and 26.8% +/- 2.6%, respectively. Western blotting further confirmed that both MCPs inhibit MAP kinase activation, increase the expression level of its downstream target Bim, a pro-apoptotic protein, and induce the cleavage of Caspase-3 in PC3 and CASP1.1 prostate cancer cells.. PectaSol MCP and PectaSol-C MCP can inhibit cell proliferation and apoptosis in prostate cancer cell lines. Our data suggested that 1.0% PectaSol-C can be used for further chemopreventive and chemotherapeutic analysis in vivo.

Topics: Androgens; Animals; Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Citrus; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Pectins; Prostatic Hyperplasia; Prostatic Neoplasms

Treatment options for androgen-independent prostate cancer cells are limited. Therefore, it is critical to identify agents that induce death of both androgen-responsive and androgen-insensitive cells. Here we demonstrate that a product of plant cell walls, pectin, is capable of inducing apoptosis in androgen-responsive (LNCaP) and androgen-independent (LNCaP C4-2) human prostate cancer cells. Commercially available fractionated pectin powder (FPP) induced apoptosis (approximately 40-fold above non-treated cells) in both cell lines as determined by the Apoptosense assay and activation of caspase-3 and its substrate, poly(ADP-ribose) polymerase. Conversely, citrus pectin (CP) and the pH-modified CP, PectaSol, had little or no apoptotic activity. Glycosyl residue composition and linkage analyses revealed no significant differences among the pectins. Mild base treatment to remove ester linkages destroyed FPP's apoptotic activity and yielded homogalacturonan (HG) oligosaccharides. The treatment of FPP with pectinmethylesterase to remove galacturonosyl carboxymethylesters and/or with endopolygalacturonase to cleave nonmethylesterified HG caused no major reduction in apoptotic activity, implicating the requirement for a base-sensitive linkage other than the carboxymethylester. Heat treatment of CP (HTCP) led to the induction of significant levels of apoptosis comparable to FPP, suggesting a means for generating apoptotic pectic structures. These results indicate that specific structural elements within pectin are responsible for the apoptotic activity, and that this structure can be generated, or enriched for, by heat treatment of CP. These findings provide the foundation for mechanistic studies of pectin apoptotic activity and a basis for the development of pectin-based pharmaceuticals, nutraceuticals, or recommended diet changes aimed at combating prostate cancer occurrence and progression.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cells, Cultured; Endothelial Cells; Humans; Hydrogen-Ion Concentration; Male; Oligosaccharides; Pectins; Prostatic Neoplasms; Protein Denaturation

In this report, we challenge a common perception that tumor embolism is a size-limited event of mechanical arrest, occurring in the first capillary bed encountered by blood-borne metastatic cells. We tested the hypothesis that mechanical entrapment alone, in the absence of tumor cell adhesion to blood vessel walls, is not sufficient for metastatic cell arrest in target organ microvasculature. The in vivo metastatic deposit formation assay was used to assess the number and location of fluorescently labeled tumor cells lodged in selected organs and tissues following intravenous inoculation. We report that a significant fraction of breast and prostate cancer cells escapes arrest in a lung capillary bed and lodges successfully in other organs and tissues. Monoclonal antibodies and carbohydrate-based compounds (anti-Thomsen-Friedenreich antigen antibody, anti-galectin-3 antibody, modified citrus pectin, and lactulosyl-l-leucine), targeting specifically beta-galactoside-mediated tumor-endothelial cell adhesive interactions, inhibited by >90% the in vivo formation of breast and prostate carcinoma metastatic deposits in mouse lung and bones. Our results indicate that metastatic cell arrest in target organ microvessels is not a consequence of mechanical trapping, but is supported predominantly by intercellular adhesive interactions mediated by cancer-associated Thomsen-Friedenreich glycoantigen and beta-galactoside-binding lectin galectin-3. Efficient blocking of beta-galactoside-mediated adhesion precludes malignant cell lodging in target organs.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Bone Neoplasms; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Citrus; Female; Galectin 3; Humans; Leucine; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Mice, SCID; Neoplasm Metastasis; Neoplasm Transplantation; Pectins; Prostatic Neoplasms

Topics: Carotenoids; Heart Diseases; Hot Temperature; Humans; Lycopene; Male; Pectins; Periodontal Diseases; Prostatic Neoplasms

Topics: Animals; Disease Progression; Humans; Incidence; Lung Neoplasms; Male; Pectins; Prostatic Neoplasms

Prostate cancer is the most common cancer diagnosed in U.S. men and remains incurable once it has metastasized. Many stages of the metastatic cascade involve cellular interactions mediated by cell surface components, such as carbohydrate-binding proteins, including galactoside-binding lectins (galectins). Modified citrus pectin (pH-modified), a soluble component of plant fiber derived from citrus fruit, has been shown to interfere with cell-cell interactions mediated by cell surface carbohydrate-binding galectin-3 molecules.. The aim of this study was to determine whether modified citrus pectin, a complex polysaccharide rich in galactosyl residues, could inhibit spontaneous metastasis of prostate adenocarcinoma cells in the rat.. The ability of modified citrus pectin to inhibit the adhesion of Dunning rat prostate cancer MAT-LyLu cells to rat endothelial cells was measured by 51Cr-labeling. Modified citrus pectin inhibition of MAT-LyLu cell anchorage-independent growth was measured by colony formation in agarose. The presence of galectin-3 in rat MAT-LyLu cells and human prostate carcinoma was demonstrated by immunoblotting and immunohistochemistry. One million MAT-LyLu cells were injected subcutaneously into the hind limb of male Copenhagen rats on day 0. Rats were given 0.0%, 0.01%, 0.1%, or 1.0% (wt/vol) modified citrus pectin continuously in their drinking water (from day 4 until necropsy on day 30). The number of MAT-LyLu tumor colonies in the lungs were counted.. Compared with 15 or 16 control rats that had lung metastases on day 30, seven of 14 rats in the 0.1% and nine of 16 rats in the 1.0% modified citrus-pectin group had statistically significant (two-sided; P < .03 and P < .001, respectively) reductions in lung metastases. The lungs of the 1.0% modified citrus pectin-treated rats had significantly (two-sided; P < .05) fewer metastatic colonies than control groups (9 colonies +/- 4 [mean +/- SE] in the control group compared with 1 colony +/- 1 in the treated group). Modified citrus pectin had no effect on the growth of the primary tumors. In vitro, modified citrus pectin inhibited MAT-LyLu cell adhesion to rat endothelial cells in a time- and dose-dependent manner as well as their colony formation in semisolid medium.. We present a novel therapy in which oral intake of modified citrus pectin acts as a potent inhibitor of spontaneous prostate carcinoma metastasis in the Copenhagen rat.. Further investigations are warranted to determine the following: 1) the role of galectin-3 in normal and cancerous prostate tissues and 2) the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.

Topics: Adenocarcinoma; Administration, Oral; Analysis of Variance; Animals; Cell Adhesion; Cell Separation; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Immunoblotting; Immunoenzyme Techniques; Male; Neoplasm Metastasis; Pectins; Prostatic Neoplasms; Rats; Tumor Stem Cell Assay

Modified citrus pectin (MCP) added to the media of cultured androgen-independent human prostatic JCA-1 cells reduced cell growth and correspondingly [3H]thymidine incorporation into DNA, which was correlated with the down-regulation of cyclin B and p34cdc2 MCP also induced distinct increases in specific endogenous phosphoproteins, including a cAMP-stimulated 52,000 (52-kDa) protein. Since metastatis has been inversely correlated with nm23 gene expression in some cancer cells and was reportedly inhibited by MCP in a rat prostate model, we investigated steady state level changes in the nm23 protein in JCA-1 cells and found it to be unexpectedly suppressed as a result of exposure to MCP.

Topics: Animals; CDC2 Protein Kinase; Cell Division; Citrus; Cyclin D; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Cyclins; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Metastasis; Pectins; Phosphoproteins; Prostatic Neoplasms; Proto-Oncogene Proteins; Rats; Tumor Cells, Cultured; Tumor Suppressor Protein p53