Molecular Effects of 13C/DIM in Prostate Cancer
Abstract
To discover the mechanisms of 13C/DIM action on prostate cancer cells, we have investigated the molecular effects of 13C/DIM on Akt and NF- B pathways and their downstream genes which play critical roles in the control of cell survival. We have found that I3C/DIM significantly inhibited the activation of Akt in PC-3 and LNCaP prostate cancer cells. Moreover, we found that 13C/DIM also significantly inhibited the activity of NF- B. However, we did not observe such inhibitory effects of 13C/DIM on non-tumorigenic CRL-2221 prostate epithelial cells. Most importantly, we found that 13C/DIM could inhibit NF- B activation and AR transactivation in prostate cancer cells transfected with activated Akt. These results demonstrate that there is a crosstalk between Akt, NF- B, and AR signaling pathways and 13C/DIM could interrupt the crosstalk, leading to the induction of apoptosis. From transfection experiments, we found that 13C/DIM inhibited the expression of IKK , the subsequent phosphorylation of I B , and the nuclear localization and activation of NF- B. By microarray analysis, we found that 13C/DIM could regulate the expression of genes which control cell cycle, apoptosis, and signal transduction. 13C/DIM also inhibited angiogenesis and invasion. These results suggest that 13C and DIM may be potent agents for the prevention and/or treatment of prostate cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA469160
Entities
People
- Fazlul H. Sarkar
Organizations
- Wayne State University