Inhibition of N-methyl-N-nitrosourea-induced mammary tumors in rats by the soybean isoflavones

Andreas I. Constantinou, Rajendra G. Mehta, Andrew T M Vaughan

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Soy-based diets, rich in the isoflavones genistein and daidzein, are thought to protect against breast and prostate cancer. Soy-based diets, rich in the isoflavones genistein and daidzein, are thought to protect against breast and prostate cancer. We used the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis animal model to test the effectiveness of these two isoflavones as chemopreventive agents. Each isoflavone was injected daily into 35-day-old rats for six months while we monitored the animals' body weight and mammary tumor appearance. Genistein was effective in reducing tumor multiplicity, but it reduced tumor incidence only marginally. Daidzein was less effective in reducing both tumor incidence and multiplicity. To investigate genistein's mechanism of action we determined the topoisomerase II (topo II) activity and detected the phosphotyrosine-containing peptides in the extracts of mammary tissues isolated from control and isoflavone-treated animals. Mammary tumors contained over 60-fold higher topo II enzymatic activity than the mammary glands. Similarly, more tyrosine phosphopeptides were detectable in mammary tumors than in mammary glands. Tissue samples from genistein treated animals contained similar topo II and protein tyrosine kinase (PTK) activities as the control group. These data suggest that mammary tumorigenesis is accompanied by an extensive increase in topo II and PTK activities. The mechanism of chemoprevention by genistein, however, is independent of topo II or PTK inhibition.

Original languageEnglish (US)
Pages (from-to)3293-3298
Number of pages6
JournalAnticancer Research
Volume16
Issue number6 A
StatePublished - 1996
Externally publishedYes

Keywords

  • Carcinogenesis
  • Chemoprevention
  • Isoflavones
  • Protein tyrosine kinase
  • Topoisomerase II

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Inhibition of N-methyl-N-nitrosourea-induced mammary tumors in rats by the soybean isoflavones'. Together they form a unique fingerprint.

Cite this