Prevention of prostate-related cancers in Lobund-Wistar rats

Prostate. 1999 Jun 1;39(4):305-9. doi: 10.1002/(sici)1097-0045(19990601)39:4<305::aid-pros12>3.0.co;2-y.

Abstract

Background: Since prostate cancer (PC) development involves a combination of genetic predisposition and promotional mechanisms, especially the metabolic conversion of testosterone to 5alpha dihydrotestosterone (DHT) by 5alpha reductase, how do mechanisms in man relate to prostate-seminal vesicle (P-SV) tumor development in Lobund-Wistar (L-W) rats? The disease in man and in L-W rats shares developmental mechanisms and characteristics to the extent that prevention of P-SV tumors in L-W rats could be predictive of similar results in man. The epidemiology of PC in man and P-SV tumors in L-W rats indicates that both are hormone-related diseases based on genetic predisposition, high production of androgens (which are activated to DHT by 5alpha reductase), and early development of androgen-dependent and metastasizing late androgen-independent stages of adenocarcinomas, all after long latency periods.

Methods: L-W rats at risk of developing spontaneous or induced P-SV tumors were subjected to putative antitumor agents or procedures. These included dietary restriction, testosterone ablation, soybean-derived isoflavones, antiangiogenic linomide, tamoxifen, and a vitamin D analogue.

Results: L-W rats subjected to 1) early onset of dietary restriction manifested suppression of spontaneous and induced development of P-SV tumors; 2) testosterone-ablation by nonesterified DHT (NE-DHT) suppressed early onset of induced P-SV tumors and to a lesser extent late onset of spontaneous tumors; 3) diets containing soy protein isolate (high isoflavones) manifested marginal suppressive effects against induced P-SV tumors, but in 12-month-old rats, the development of spontaneous tumors was reduced in incidence; 4) early administrations of antiangiogenic linomide suppressed development of induced P-SV tumors and of transplanted prostate adenocarcinoma III (PA-III) tumors, but linomide had little antitumor effect against large advanced stage tumors; and 5) tamoxifen and vitamin D analogue suppressed development of P-SV tumors. Results in conditions 1-3 were negative when tested against PA-III tumors.

Conclusions: Developing stages of P-SV tumors were prevented in L-W rats with autochthonous spontaneous and induced tumors, but most of the agents tested were of no therapeutic benefit against advanced-stage and transplanted PA-III tumors. However, early administrations of antiangiogenic linomide suppressed early growth of induced and transplanted PA-III tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Disease Susceptibility
  • Estrogens, Non-Steroidal / therapeutic use
  • Hydroxyquinolines / therapeutic use
  • Isoflavones / therapeutic use
  • Male
  • Neovascularization, Pathologic / prevention & control
  • Phytoestrogens
  • Plant Preparations
  • Prostatic Neoplasms / diet therapy
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / prevention & control*
  • Rats
  • Rats, Wistar
  • Soybeans
  • Tamoxifen / therapeutic use
  • Testosterone / antagonists & inhibitors
  • Vitamin D / analogs & derivatives
  • Vitamin D / therapeutic use

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Estrogens, Non-Steroidal
  • Hydroxyquinolines
  • Isoflavones
  • Phytoestrogens
  • Plant Preparations
  • Tamoxifen
  • Vitamin D
  • roquinimex
  • Testosterone