Targeting Nuclear Factor kappa B for the Treatment of Prostate Cancer
Abstract
This report details our progress to date describing the inhibition of the transcription factor, Nuclear Factor kappa B (NFkB) with parthenolide. To date, we have shown that NFkB is constitutively active in prostate cancer cell lines and endothelial cells and that NFkB DNA binding is inhibited by parthenolide. Moreover, we have found that NFkB is over-expressed in human prostatectomy speciments at both the prostatic intraepithelial neoplasia and invasive adenocarcinoma stages. With the use of cDNA array technology, we have shown that multiple genes associated with the hallmarks of cancer and that are under NFkB control are decreased when cancer and endothelial cells are treated with parthenolide. We have subsequently shown that parthenolide is able to decrease cancer cell proliferation and enhance the cytotoxic effect of taxanes in vitro. Finally, we have shown that parthenolide is bioactive in vivo as it is able to inhibit angiogenesis as a single agent, enhance the cytotoxic effects of docetaxel and restore sensitivity of the hormone independent cell line, CWR22Rvl, to the anti-androgen, bicalutamide.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA425799
Entities
People
- Christopher J. Sweeney
Organizations
- Indiana University