Antiproliferative and antiangiogenic activities of genistein in human renal cell carcinoma☆
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.
aDepartment of Urology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan
Reprint requests: Atsushi Takahashi, M.D., Department of Urology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan
☆ 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.
ABSTRACT