Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study.
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.
Prostate Cancer Prostatic Dis. 2003;6(4):301-4
Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin.
BACKGROUND: The role of dietary components in cancer progression and metastasis is an emerging field of clinical importance. Many stages of cancer progression involve carbohydrate-mediated recognition processes. We therefore studied the effects of high pH- and temperature-modified citrus pectin (MCP), a nondigestible, water-soluble polysaccharide fiber derived from citrus fruit that specifically inhibits the carbohydrate-binding protein galectin-3, on tumor growth and metastasis in vivo and on galectin-3-mediated functions in vitro. METHODS: In vivo tumor growth, angiogenesis, and metastasis were studied in athymic mice that had been fed with MCP in their drinking water and then injected orthotopically with human breast carcinoma cells (MDA-MB-435) into the mammary fat pad region or with human colon carcinoma cells (LSLiM6) into the cecum. Galectin-3-mediated functions during tumor angiogenesis in vitro were studied by assessing the effect of MCP on capillary tube formation by human umbilical vein endothelial cells (HUVECs) in Matrigel. The effects of MCP on galectin-3-induced HUVEC chemotaxis and on HUVEC binding to MDA-MB-435 cells in vitro were studied using Boyden chamber and labeling assays, respectively. The data were analyzed by two-sided Student’s t test or Fisher’s protected least-significant-difference test. RESULTS: Tumor growth, angiogenesis, and spontaneous metastasis in vivo were statistically significantly reduced in mice fed MCP. In vitro, MCP inhibited HUVEC morphogenesis (capillary tube formation) in a dose-dependent manner. In vitro, MCP inhibited the binding of galectin-3 to HUVECs: At concentrations of 0.1% and 0.25%, MCP inhibited the binding of galectin-3 (10 micro g/mL) to HUVECs by 72.1% (P =.038) and 95.8% (P =.025), respectively, and at a concentration of 0.25% it inhibited the binding of galectin-3 (1 micro g/mL) to HUVECs by 100% (P =.032). MCP blocked chemotaxis of HUVECs toward galectin-3 in a dose-dependent manner, reducing it by 68% at 0.005% (P<.001) and inhibiting it completely at 0.1% (P<.001). Finally, MCP also inhibited adhesion of MDA-MB-435 cells, which express galectin-3, to HUVECs in a dose-dependent manner. CONCLUSIONS: MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effects on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.
J Natl Cancer Inst. 2002 Dec 18;94(24):1854-62
Effects of natural complex carbohydrate (citrus pectin) on murine melanoma cell properties related to galectin-3 functions.
Citrus pectin (CP) and pH-modified citrus pectin (MCP) are highly branched and non-branched complex polysaccharides, respectively, rich in galactoside residues, capable of combining with the carbohydrate-binding domain of galectin-3. We reported previously that intravenous injection of B16-F1 murine melanoma cells with CP or MCP into syngeneic mice resulted in a significant increase or decrease of lung colonization, respectively (Platt D, Raz A (1992) J Natl Cancer Inst 84:438-42). Here we studied the effects of these polysaccharides on cell-cell and cell-matrix interactions mediated by carbohydrate-recognition. MCP, but not CP, inhibited B16-F1 melanoma cells adhesion to laminin and asialofetuin-induced homotypic aggregation. Both polysaccharides inhibited anchorage-independent growth of B16-F1 cells in semisolid medium, i.e. agarose. These results indicate that carbohydrate-recognition by cell surface galectin-3 may be involved in cell-extracellular matrix interaction and play a role in anchorage-independent growth as well as the in vivo embolization of tumour cells.
Glycoconj J. 1994 Dec;11(6):527-32
Modified citrus pectin anti-metastatic properties: one bullet, multiple targets.
In this minireview, we examine the ability of modified citrus pectin (MCP), a complex water soluble indigestible polysaccharide obtained from the peel and pulp of citrus fruits and modified by means of high pH and temperature treatment, to affect numerous rate-limiting steps in cancer metastasis. The anti-adhesive properties of MCP as well as its potential for increasing apoptotic responses of tumor cells to chemotherapy by inhibiting galectin-3 anti-apoptotic function are discussed in the light of a potential use of this carbohydrate-based substance in the treatment of multiple human malignancies.
Carbohydr Res. 2009 Sep 28;344(14):1788-91
Extraction of green labeled pectins and pectic oligosaccharides from plant byproducts.
Green labeled pectins were extracted by an environmentally friendly way using proteases and cellulases being able to act on proteins and cellulose present in cell walls. Pectins were isolated from different plant byproducts, i.e., chicory roots, citrus peel, cauliflower florets and leaves, endive, and sugar beet pulps. Enzymatic extraction was performed at 50 degrees C for 4 h, in order to fulfill the conditions required for microbiological safety of extracted products. High methoxy (HM) pectins of high molar mass were extracted with three different enzyme mixtures. These pectins were subsequently demethylated with two pectin methyl esterases (PMEs), either the fungal PME from Aspergillus aculeatus or the orange PME. It was further demonstrated that high molar mass low methoxy (LM) pectins could also be extracted directly from cell walls by adding the fungal PME to the mixture of protease and cellulase. Moreover, health benefit pectic oligosaccharides, the so-called modified hairy regions, were obtained after enzymatic treatment of the residue recovered after pectin extraction. The enzymatic method demonstrates that it is possible to convert vegetable byproducts into high-added value compounds, such as pectins and pectic oligosaccharides, and thus considerably reduce the amount of these residues generated by food industries.
J Agric Food Chem. 2008 Oct 8;56(19):8926-35
Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c mice.
The health benefits of fruits and vegetables have been the subject of numerous investigations over many years. Two natural substances, quercetin (a flavonoid) and citrus pectin (a polysaccharide found in the cell wall of plants) are of particular interest to cancer researchers. Two modified versions of these substances - quercetin chalcone (QC) and a pH-modified citrus pectin (MCP) - are the focus of this study. Previous research has confirmed that quercetin exhibits antitumor properties, likely due to immune stimulation, free radical scavenging, alteration of the mitotic cycle in tumor cells, gene expression modification, anti-angiogenesis activity, or apoptosis induction, or a combination of these effects. MCP has inhibited metastases in animal studies of prostate cancer and melanoma. To date, no study has demonstrated a reduction in solid tumor growth with MCP, and there is no research into the antitumor effect of QC. This study examines the effects of MCP and QC on the size and weight of colon-25 tumors implanted in balb-c mice. Fifty mice were orally administered either 1 ml distilled water (controls), low-dose QC (0.8 mg/ml), high-dose QC (1.6 mg/ml), low-dose MCP (0. 8 mg/ml) or high-dose MCP (1.6 mg/ml) on a daily basis, beginning the first day of tumor palpation (usually eight days post-implantation). A significant reduction in tumor size was noted at day 20 in all groups compared to controls. The groups given low-dose QC and MCP had a 29% (NS) and 38% (p<0.02) decrease in size, respectively. The high-dose groups had an even more impressive reduction in size; 65% in the QC group and 70% in the mice given MCP (both p<0.001). This is the first evidence that MCP can reduce the growth of solid primary tumors, and the first research showing QC has antitumor activity. Additional research on these substances and their effect on human cancers is warranted.
Altern Med Rev. 2000 Dec;5(6):546-52
Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model.
AIM: To discuss the expression of glactin-3 in liver metastasis of colon cancer and its inhibition by modified citrus pectin (MCP) in mice. METHODS: Seventy-five Balb/c mice were randomly divided into negative control group (n = 15), positive control group (n = 15), low MCP concentration group (n = 15), middle MCP concentration group (n = 15) and high MCP concentration group (n = 15). CT26 colon cancer cells were injected into the subcapsule of mouse spleen in positive control group, low, middle and high MCP concentrations groups, except in negative control, to set up a colon cancer liver metastasis model. The concentration of MCP in drinking water was 0.0%, 0.0%, 1.0%, 2.5% and 5.0% (wt/vol), respectively. Liver metastasis of colon cancer was observed after 3 wk. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of galectin-3 in serum. Expression of galectin-3 in liver metastasis was detected by immunohistochemistry. RESULTS: Except for the negative group, the percentage of liver metastasis in the other 4 groups was 100%, 80%, 73.3% and 60%, respectively. The number of liver metastases in high MCP concentration group was significantly less than that in positive control group (P = 0.008). Except for the negative group, the median volume of implanted spleen tumor in the other 4 groups was 1.51 cm(3), 0.93 cm(3), 0.77 cm(3) and 0.70 cm(3), respectively. The volume of implanted tumor in middle and high MCP concentration groups was significantly smaller than that in positive control group (P = 0.019; P = 0.003). The concentration of serum galectin-3 in positive control and MCP treatment groups was significantly higher than that in the negative control group. However, there was no significant difference between them. Except for the negative control group, the expression of galectin-3 in liver metastases of the other 4 groups showed no significant difference. CONCLUSION: Expression of galetin-3 increases significantly in liver metastasis of colon cancer, which can be effectively inhibited by MCP.
World J Gastroenterol. 2008 Dec 28;14(48):7386-91
Expression of galectin-3 in liver metastasis of colon cancer and the inhibitory effect of modified citrus pectin.
OBJECTIVE: To observe the expression of galectin-3 in the liver metastasis of colon cancer in mice and the inhibitory effect of modified citrus pectin (MCP) on galectin-3 expression. METHODS: Seventy-five Balb/c mice were randomized into 5 groups, namely the negative control, positive control, low-concentration MCP, moderate-concentration MCP and high-concentration MCP groups. CT26 colon cancer cells were injected into the subcapsule of the mouse spleen to establish liver metastasis models of colon cancer, but the mice in the negative control group received no tumor cell injection. MCP was added into the drinking water of the mice at the concentrations of 0, 1.0%, 2.5% and 5.0% (m/V). The liver metastasis was observed 3 weeks after tumor cell inoculation. Enzyme-linked immunosorbent assay was performed to determine the serum galectin-3 level. A tissue microarray of the liver metastasis was prepared for immunohistochemical detection of galectin-3 expression in the liver metastasis. RESULTS: In the positive control, low-, moderate- and high-concentration MCP groups, the rates of liver metastasis were 100%, 80%, 73.3% and 60%, respectively. The number of liver metastases in high-concentration MCP group was significantly smaller than that in the positive control group (P<0.05). In the 4 groups with tumor cell inoculation, the median volume of the primary lesions in the spleen was 1.51, 0.93, 0.77 and 0.70 cm(3), respectively, which were significantly smaller in the moderate- and high-concentration MCP groups than in the positive control group (P<0.05). The serum galectin-3 level in the positive control group and MCP-treated groups were significantly higher than that in the negative control group (P<0.01), but similar between the positive control group and the MCP-treated groups (P>0.05). In the positive control and the MCP-treated groups, the expression of galectin-3 in the liver metastases showed no significant differences (P>0.05). CONCLUSION: The expression of galetin-3 is significantly increased in the liver metastasis of colon cancer, and MCP can effectively inhibit the liver metastasis.
Nan Fang Yi Ke Da Xue Xue Bao. 2008 Aug;28(8):1358-61
Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs.
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.
Neoplasia. 2005 May;7(5):522-7
Death receptor agonists as a targeted therapy for cancer.
Apoptosis is integral to normal, physiologic processes that regulate cell number and results in the removal of unnecessary or damaged cells. Apoptosis is frequently dysregulated in human cancers, and recent advancements in our understanding of the regulation of programmed cell death pathways has led to the development of novel agents to reactivate apoptosis in malignant cells. The activation of cell surface death receptors by tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) and death receptor agonists represent an attractive therapeutic strategy to promote apoptosis of tumor cells through the activation of the extrinsic pathway. The observation that Apo2L/TRAIL can eliminate tumor cells preferentially over normal cells has resulted in several potential therapeutics that exploit the extrinsic pathway, in particular, the soluble recombinant human (rh)Apo2L/TRAIL protein and agonist monoclonal antibodies that target death receptors 4 or 5. Many of these agents are currently being evaluated in phase 1 or 2 trials, either as a single agent or in combination with cytotoxic chemotherapy or other targeted agents. The opportunities and challenges associated with the development of death receptor agonists as cancer therapeutics, the status of ongoing clinical evaluations, and the progress toward identifying predictive biomarkers for patient selection and pharmacodynamic markers of response are reviewed.
Clin Cancer Res. 2010 Mar 15;16(6):1701-8
PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and- independent prostate cancer cells.
AIM: To demonstrate the efficacy of PectaSol-C modified citrus pectin (MCP) on prostate cancer in vitro. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
Integr Cancer Ther. 2010 Jun;9(2):197-203