title: Inhibition of human breast cancer growth by GCP (genistein combined polysaccharide) in xenogeneic athymic mice: involvement of genistein biotransformation by beta-glucuronidase from tumor tissues.
abstract: The role of beta-glucuronidase in genistein biotransformation was investigated in a human breast cancer MDA-MB-231 xenogeneic athymic mouse model. Genistein combined polysaccharide (GCP), a genistein aglycone rich functional food supplement was used in these experiments. Tumor-bearing mice were subjected to oral administration of GCP for 28 days. GCP treatment significantly inhibited tumor growth. Induction of apoptosis by GCP treatment was related to activation of cleavage of poly(ADP-ribose)polymerase, induction of the p21 protein expression and reduction of cyclin B1 expression in the tumor tissues. Genistein exists as a glucuronide conjugate in normal organ tissues, and the conjugated genistein lacks the physiological activity of the aglycone. Tumor tissues contain large amounts of beta-glucuronidase, the enzyme that converts the genistein beta-glucuronide conjugate into genistein aglycone. The resulting genistein aglycone exerts its chemopreventive activities, including the induction of apoptosis in tumor tissues, and, finally, leads to tumor growth inhibition.
authors.affiliation: Laboratory of Biochemistry, Amino Up Chemical Co Ltd, Sapporo 004-0839, Japan. yuanlan@hotmail.com
authors.forename: Lan
authors.initials: L
authors.lastname: Yuan
authors.forename: Chihiro
authors.initials: C
authors.lastname: Wagatsuma
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Takehito
authors.initials: T
authors.lastname: Miura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Mukoda
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujii
authors.forename: Buxiang
authors.initials: B
authors.lastname: Sun
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011134:Polysaccharides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011134:Polysaccharides; C473311:genistein combined polysaccharide; D019833:Genistein; D005966:Glucuronidase