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.
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.
Yuan
Lan
L
Laboratory of Biochemistry, Amino Up Chemical Co Ltd, Sapporo 004-0839, Japan. yuanlan@hotmail.com
Wagatsuma
Chihiro
C
Yoshida
Mayumi
M
Miura
Takehito
T
Mukoda
Tomomi
T
Fujii
Hajime
H
Sun
Buxiang
B
Kim
Jung-Hwan
JH
Surh
Young-Joon
YJ
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
D000970:Antineoplastic Agents; D011134:Polysaccharides; C473311:genistein combined polysaccharide; D019833:Genistein; D005966:Glucuronidase