Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels.
Silibinin, a flavonolignan from milk thistle seeds, possesses cancer chemopreventive properties in rodent models of carcinogenesis. We tested the hypotheses that silibinin or silipide, silibinin formulated with phospholipids, delays tumour development in TRAMP or Apc(Min) mice, genetic models of prostate or intestinal malignancies, respectively. Mice received silibinin or silipide with their diet (0.2% silibinin equivalents) from weaning. Intervention with silipide reduced the size of well differentiated TRAMP adenocarcinomas by 31%. Silipide and silibinin decreased the incidence of poorly differentiated carcinomas by 61% compared to mice on control diet. Silipide decreased plasma levels of insulin-like growth factor (IGF)-1 by 36%. Levels of circulating IGF binding protein (IGFBP)-3 in mice on silipide or silibinin were 3.9- or 5.9-fold, respectively, elevated over those in control TRAMP mice. In Apc(Min) mice silibinin, but not silipide, had only a marginal adenoma number-reducing effect. The results cautiously support the advancement of silipide to the stage of clinical investigation in prostate cancer.
Verschoyle
Richard D
RD
Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, RKCSB, LRI, University of Leicester, Leicester LE2 7LX, UK.
Greaves
Peter
P
Patel
Ketan
K
Marsden
Debbie A
DA
Brown
Karen
K
Steward
William P
WP
Gescher
Andreas J
AJ
D000236:Adenoma / Q000097:blood / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000097:blood / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000097:blood / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000097:blood / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000097:blood / Q000517:prevention & control*; D000077385:Silybin; D012838:Silymarin / Q000097:blood / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D010713:Phosphatidylcholines; D012838:Silymarin; C067772:IdB 1016; D000077385:Silybin; D007334:Insulin-Like Growth Factor I