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学科主题: 临床医学
题名:
Galbanic acid decreases androgen receptor abundance and signaling and induces G(1) arrest in prostate cancer cells
作者: Zhang, Yong2,3,4; Kim, Kwan-Hyun1,2; Zhang, Wei5; Guo, Yinglu3,4; Kim, Sung-Hoon1,2; Lu, Junxuan2
关键词: galbanic acid ; androgen receptor ; proteasomal degradation ; prostate cancer ; G(1) arrest
刊名: INTERNATIONAL JOURNAL OF CANCER
发表日期: 2012
DOI: 10.1002/ijc.25993
卷: 130, 期:1, 页:200-212
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: TRANSGENIC ADENOCARCINOMA ; METHYLSELENINIC ACID ; DNA-REPLICATION ; CDK INHIBITORS ; CYCLE ARREST ; CARCINOGENESIS ; ANTIANDROGEN ; INDUCTION ; GROWTH ; APOPTOSIS
英文摘要:

Androgen receptor (AR) signaling is crucial for the genesis and progression of prostate cancer (PCa). We compared the growth responses of AR(+) LNCaP and LNCaP C4-2 vs. AR(-) DU145 and PC-3 PCa cell lines to galbanic acid (GBA) isolated from the resin of medicinal herb Ferula assafoetida and assessed their connection to AR signaling and cell cycle regulatory pathways. Our results showed that GBA preferentially suppressed AR(+) PCa cell growth than AR(-) PCa cells. GBA induced a caspase-mediated apoptosis that was attenuated by a general caspase inhibitor. Subapoptotic GBA downregulated AR protein in LNCaP cells primarily through promoting its proteasomal degradation, and inhibited AR-dependent transcription without affecting AR nuclear translocation. Whereas docking simulations predicted binding of GBA to the AR ligand binding domain with similarities and differences with the AR antagonist drug bicalutamide (Bic), LNCaP cell culture assays did not detect agonist activity of GBA. GBA and Bic exerted greater than additive inhibitory effect on cell growth when used together. Subapoptotic GBA induced G(1) arrest associated with an inhibition of cyclin/CDK4/6 pathway, especially cyclin D-1 without the causal involvement of cyclin-dependent kinase (CDK) inhibitory proteins P21(Cip1) and P27(Kip1). In summary, the novelty of GBA as an anti-AR compound resides in the distinction between GBA and Bic with respect to AR protein turnover and a lack of agonist effect. Our observations of anti-AR and cell cycle arrest actions plus the anti-angiogenesis effect reported elsewhere suggest GBA as a multitargeting drug candidate for the prevention and therapy of PCa.

语种: 英语
所属项目编号: CA136953 ; 2009-0063466
项目资助者: NIH ; Korean Medical Research Center (MRC) ; Hormel Foundation
WOS记录号: WOS:000297851300021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61392
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Peking Univ, Inst Urol, Hosp 1, Beijing 100871, Peoples R China
2.So Res Inst, Birmingham, AL 35255 USA
3.Kyung Hee Univ, Coll Oriental Med, Canc Prevent Mat Dev Res Ctr, Seoul 131701, South Korea
4.Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
5.Peking Univ, Natl Urol Canc Ctr, Hosp 1, Beijing 100871, Peoples R China

Recommended Citation:
Zhang, Yong,Kim, Kwan-Hyun,Zhang, Wei,et al. Galbanic acid decreases androgen receptor abundance and signaling and induces G(1) arrest in prostate cancer cells[J]. INTERNATIONAL JOURNAL OF CANCER,2012,130(1):200-212.
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