Dual-Targeting of AR and Akt Pathways by Berberine in Castration-Resistant Prostate Cancer
Abstract
We have previously shown berberine, a natural compound, downregulates full-length androgen receptor (AR) and AR splice variants lacking the ligand-binding domain. During this grant period, we set out to investigate the underlying mechanisms. We found that berberine reduced full-length AR by inhibiting AR transcription, and inducing AR poly-ubiquitination, leading to protein degradation via the proteasome pathway. In contrast, the suppressive action on AR splice variants was exerted mainly through its inhibition of AR transcription, as berberine did not influence the degradation of the splice variants. We also found that these variants were intrinsically unstable, having a half-life much shorter than that of full-length AR. This could lead to a rapid depletion of the splice variants when protein synthesis is halted by berberine due to its reduction of AR transcripts. Additionally, we tested the efficacy of berberine in a Pten knockout model. We found that berberine inhibited tumor growth, but had no adverse effects on normal organs. Since Pten loss or inactivation is common in prostate cancer, these results provide support for the use of berberine in the prevention and treatment of prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2013
- Accession Number
- ADA593307
Entities
People
- Haitao Zhang
Organizations
- Tulane University of Louisiana