Inhibitory effect of genistein on mouse colon cancer MC-26 cells involved TGF-{beta}1/Smad pathway
- School of Public Health, Zhengzhou University, Zhengzhou 450052 (China)
- Laboratory of Neuroimmunology, Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7025 (United States)
TGF-{beta}1/signaling has been shown to be associated with proapoptotic and antimitotic activities in epithelial tissues. Genistein, a major component of soybean isoflavone, has multiple functions resulting in anticancer proliferation. We herein showed that genistein dose-dependently increased TGF-{beta}1 mRNA expression in mouse colon cancer MC-26 cells. A mouse monoclonal anti-TGF-{beta}1 neutralizing antibody partially, but not completely, blocked the growth inhibition by genistein. By using adenoviral vector, we demonstrated that Smad7 overexpression attenuated genistein-induced growth inhibition and apoptosis as determined by MTT and apoptosis ELISA. Smad7 overexpression also inhibited upregulation of p21 and caspase-3 activity by geinistein. To further confirm inhibitory effect of genistein in MC-26 cells require TGF-{beta}1/Smad signaling, we employed Western blot and electrophoretic mobility shift assay to detect formation of Smad-DNA complexes and phosphorylation of Smad2 and Smad3, respectively. Data revealed that genistein induced an evident formation of Smad-DNA complexes and phosphorylation of Smad2 and Smad3, indicating increased TGF-{beta}1 signaling. Taken together, these findings first provided insights into possible molecular mechanisms of growth inhibition by genistein that required Smad signaling, which could aid in its evaluation for colon tumor prevention.
- OSTI ID:
- 20710882
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 333; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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