Tanshinones inhibit androgen‐dependent prostate cancer via downregulation of aurora A and suppression of androgen‐receptor signaling
Abstract
The objective of this study was to evaluate the effect of tanshinones on androgen‐dependent prostate cancer. Tanshinone I (T1), tanshinone IIA and cryptotanshinone (CT) significantly inhibited proliferation of androgen‐sensitive LNCaP cells in part via induction of apoptosis and cell cycle arrest at G0/G1 phase associated with and down‐regulation of survivin and aurora kinase expression and interference of androgen signaling pathway. Knockdown of aurora A by siRNA significantly reduced the growth‐inhibitory activity of tanshinones, suggesting aurora A as a functional target for tanshinones. Without changing the androgen receptor level, tanshinones dramatically down‐regulated gene expression of prostatic specific antigen and Nkx3.1, but upregulated maspin gene expression. The animal study using an orthotopic prostate tumor mouse model further confirmed that CT and T1 treatment significantly reduced tumor growth associated with induced prostate cancer cell apoptosis, reduced prostate cancer cell proliferation and tumor angiogenesis, down‐regulated prostate cancer cell survivin and aurora A protein expression, without altering food intake or body weight. Our results suggest that CT and T1 may be efficacious and safe candidate agents for the prevention and therapy of androgen‐sensitive prostate cancer. Supported by Idea Award PC073988 (Department of Defense).
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2012
- Source ID
- 10.1096/fasebj.26.1_supplement.363.2
Entities
People
- George Blackburn
- Hamid Abdolmaleky
- Jin-rong Zhou
- Yi Gong
Organizations
- Harvard Medical School
- United States Department of Defense