title: Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin.
abstract: 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.
authors.affiliation: Wayne State University, School of Medicine, and Department of Pathology, Karmanos Cancer Institute, Detroit, MI, USA.
authors.forename: Pratima
authors.initials: P
authors.lastname: Nangia-Makker
authors.forename: Victor
authors.initials: V
authors.lastname: Hogan
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Honjo
authors.forename: Sara
authors.initials: S
authors.lastname: Baccarini
authors.forename: Larry
authors.initials: L
authors.lastname: Tait
authors.forename: Robert
authors.initials: R
authors.lastname: Bresalier
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy; D002633:Chemotaxis; D002957:Citrus; D003110:Colonic Neoplasms / Q000188:drug therapy; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular; D019084:Fluorescent Antibody Technique, Indirect; D037502:Galectin 3 / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010368:Pectins / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D037502:Galectin 3; D011994:Recombinant Proteins; D010368:Pectins