Urology
Volume 64, Issue 2 , Pages 389-393, August 2004

Antiproliferative and antiangiogenic activities of genistein in human renal cell carcinoma

  • Hiroto Sasamura

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
  • ,
  • Atsushi Takahashi

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
    • Corresponding Author InformationReprint requests: Atsushi Takahashi, M.D., Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan
  • ,
  • Jinyang Yuan

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
  • ,
  • Hiroshi Kitamura

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
  • ,
  • Naoya Masumori

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
  • ,
  • Noriomi Miyao

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
  • ,
  • Naoki Itoh

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
  • ,
  • Taiji Tsukamoto

      Affiliations

    • Department of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan

Received 29 December 2003; accepted 29 March 2004.

Abstract 

Objectives

To determine whether genistein, an isoflavone that is plentiful in soy beans, could inhibit the growth of human renal cell carcinoma (RCC) cells in vitro, induce apoptosis, and suppress neovascularization in vivo induced by human RCC cells.

Methods

We investigated the effect of genistein on cell proliferation in four human RCC cell lines, SMKT R-1, R-2, R-3, and R-4. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay was performed to examine whether genistein could induce apoptosis in SMKT R-1 cells. To evaluate the effect of genistein on in vivo angiogenesis, we used a new mouse dorsal air sac model in which we could evaluate it simply and quantitatively. Radioisotope-labeled red blood cells were injected into a tail vein in mice bearing a Millipore filter chamber containing genistein, and the vascular volume was examined by measuring the radioactivity of the mouse dorsal skin.

Results

Treatment with genistein for 48 hours inhibited cell proliferation in a dose-dependent manner and 100 μg/mL genistein inhibited it in a time-dependent manner. A dose of 50 μg/mL genistein clearly induced cell apoptosis. The vascular volume after implantation of the Millipore filter chamber containing RCC cells increased to threefold that without RCC cells. Genistein in the Millipore filter chamber significantly decreased the neovascularization induced by human RCC cells in vivo.

Conclusions

The results of this study demonstrated that genistein inhibited cell proliferation, induced apoptosis, and suppressed in vivo angiogenesis in human RCC cells. Genistein may be a promising antitumorigenic and antiangiogenic agent for the treatment and prevention of RCC.

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 This work was supported in part by a Grant-in-Aid from the Japanese Ministry of Education, Science, Sports and Culture, and the Stiftelsen Japanese-Swedish Cooperative Research Foundation.

PII: S0090-4295(04)00417-0

doi:10.1016/j.urology.2004.03.045

Urology
Volume 64, Issue 2 , Pages 389-393, August 2004