Dietary genistein inhibits metastasis of human prostate cancer in mice

Minalini Lakshman, Li Xu, Vijayalakshmi Ananthanarayanan, Joshua Cooper, Chris H. Takimoto, Irene Helenowski, Jill C. Pelling, Raymond Bergan

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Dietary genistein has been linked to lower prostate cancer (PCa) mortality. Metastasis is the ultimate cause of death from PCa. Cell detachment and invasion represent early steps in the metastatic cascade. We had shown that genistein inhibits PCa cell detachment and cell invasion in vitro. Genistein-mediated inhibition of activation of focal adhesion kinase (FAK) and of the p38 mitogen-activated protein kinase (MAPK)-heat shock protein 27 (HSP27) pathway has been shown by us to regulate PCa cell detachment and invasion effects, respectively. To evaluate the antimetastatic potential of genistein, we developed an animal model suited to evaluating antimetastatic drug efficacy. Orthotopically implanted human PC3-M PCa cells formed lung micrometastasis by 4 weeks in >80% of inbred athymic mice. Feeding mice dietary genistein before implantation led to blood concentrations similar to those measured in genistein-consuming men. Genistein decreased metastases by 96%, induced nuclear morphometric changes in PC3-M cells indicative of increased adhesion (i.e., decreased detachment) but did not alter tumor growth. Genistein increased tumor levels of FAK, p38 MAPK, and HSP27 "promotility" proteins. However, the ratio of phosphorylated to total protein trended downward, indicating a failure to increase relative amounts of activated protein. This study describes a murine model of human PCa metastasis well suited for testing antimetastatic drugs. It shows for the first time that dietary concentrations of genistein can inhibit PCa cell metastasis. Increases in promotility proteins support the notion of cellular compensatory responses to antimotility effects induced by therapy. Studies of antimetastatic efficacy in man are warranted and are under way.

Original languageEnglish (US)
Pages (from-to)2024-2032
Number of pages9
JournalCancer Research
Volume68
Issue number6
DOIs
StatePublished - Mar 15 2008
Externally publishedYes

Fingerprint

Genistein
Prostatic Neoplasms
Neoplasm Metastasis
HSP27 Heat-Shock Proteins
Focal Adhesion Protein-Tyrosine Kinases
p38 Mitogen-Activated Protein Kinases
Proteins
Neoplasm Micrometastasis
Nude Mice
Pharmaceutical Preparations
Cause of Death
Neoplasms
Animal Models
Lung
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lakshman, M., Xu, L., Ananthanarayanan, V., Cooper, J., Takimoto, C. H., Helenowski, I., ... Bergan, R. (2008). Dietary genistein inhibits metastasis of human prostate cancer in mice. Cancer Research, 68(6), 2024-2032. https://doi.org/10.1158/0008-5472.CAN-07-1246

Dietary genistein inhibits metastasis of human prostate cancer in mice. / Lakshman, Minalini; Xu, Li; Ananthanarayanan, Vijayalakshmi; Cooper, Joshua; Takimoto, Chris H.; Helenowski, Irene; Pelling, Jill C.; Bergan, Raymond.

In: Cancer Research, Vol. 68, No. 6, 15.03.2008, p. 2024-2032.

Research output: Contribution to journalArticle

Lakshman, M, Xu, L, Ananthanarayanan, V, Cooper, J, Takimoto, CH, Helenowski, I, Pelling, JC & Bergan, R 2008, 'Dietary genistein inhibits metastasis of human prostate cancer in mice', Cancer Research, vol. 68, no. 6, pp. 2024-2032. https://doi.org/10.1158/0008-5472.CAN-07-1246
Lakshman M, Xu L, Ananthanarayanan V, Cooper J, Takimoto CH, Helenowski I et al. Dietary genistein inhibits metastasis of human prostate cancer in mice. Cancer Research. 2008 Mar 15;68(6):2024-2032. https://doi.org/10.1158/0008-5472.CAN-07-1246
Lakshman, Minalini ; Xu, Li ; Ananthanarayanan, Vijayalakshmi ; Cooper, Joshua ; Takimoto, Chris H. ; Helenowski, Irene ; Pelling, Jill C. ; Bergan, Raymond. / Dietary genistein inhibits metastasis of human prostate cancer in mice. In: Cancer Research. 2008 ; Vol. 68, No. 6. pp. 2024-2032.
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