No potential conflicts of interest were disclosed.
In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: Involvement of Nrf2 and cell cycle/apoptosis signaling pathways†
Article first published online: 11 AUG 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 51, Issue 10, pages 761–770, October 2012
How to Cite
Wu, T.-Y., Saw, C. L.-L., Khor, T. O., Pung, D., Boyanapalli, S. S.S. and Kong, A.-N. T. (2012), In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: Involvement of Nrf2 and cell cycle/apoptosis signaling pathways. Mol. Carcinog., 51: 761–770. doi: 10.1002/mc.20841
- Issue published online: 11 SEP 2012
- Article first published online: 11 AUG 2011
- Manuscript Accepted: 13 JUL 2011
- Manuscript Revised: 11 JUL 2011
- Manuscript Received: 27 MAY 2011
- phase II detoxifying/ antioxidant enzymes;
- prostate cancer;
- TRAMP mice
Indole-3-carbinol (I3C) found abundantly in crucifers has been shown to possess anti-cancer effects. The present study aims to examine the chemopreventive effects and the molecular mechanism of I3C, particularly the anti-oxidative stress pathway regulated by nuclear erythroid related factor 2 (Nrf2). HepG2-C8-ARE-luciferase cells were used for Nrf2-ARE activity. TRAMP C1 cells were used to investigate the effects of I3C on Nrf2-mediated genes. To test the chemopreventive efficacy of I3C, transgenic adenocarcinoma of mouse prostate (TRAMP) mice were fed with 1% I3C supplemented diet for 12 or 16 wk. The expression of Nrf2 and its downstream target genes, cell cycle and apoptosis genes were investigated using quantitative real-time polymerase chain reaction (qPCR). The protein expressions of these biomarkers were also investigated using Western blotting. I3C induced antioxidant response element (ARE)-luciferase activity in a dose-dependent manner. Treatments of TRAMP C1 cells with I3C also resulted in the induction of Nrf2-mediated genes. I3C significantly suppressed the incidence of palpable tumor and reduced the genitourinary weight in TRAMP mice. Western blots and qPCR analyses of prostate tissues showed that I3C induced the expression of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO-1) as well as cell cycle and apoptosis related biomarkers in I3C-fed TRAMP mice. This study demonstrated that the effectiveness of I3C as prostate cancer chemoprevention agent via up-regulation of a novel Nrf2-mediated anti-oxidative stress pathway. © 2011 Wiley Periodicals, Inc.