Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec 15;129(12):2916-27.
doi: 10.1002/ijc.25949. Epub 2011 Apr 7.

Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway

Vijayalakshmi Thamilselvan  1 , Mani Menon, Sivagnanam Thamilselvan
Affiliations

Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway

Vijayalakshmi Thamilselvan et al. Int J Cancer. .

Abstract

Activation of survival pathways has been associated with chemoresistance and progression of androgen independence which places a major obstacle to successful treatment of metastatic prostate cancer. Deguelin, a rotenoid isolated from Mundulea sericea, has an anticancer effect against several types of cancers; however, the mechanism of its antitumor effects on prostate cancer is not well understood. The aim of our study was to elucidate the effect of deguelin on the growth of prostate cancer cells and its putative mechanism of action. Deguelin decreased the viability of both androgen-dependent and -independent prostate cancer cells but not normal prostate epithelial cells. Downregulation of phosphorylated Akt and GSK-3β by deguelin promoted proteosomal degradation of β-catenin that resulted in decreased nuclear accumulation and inhibited transactivation of β-catenin-responsive genes. Deguelin-induced downregulation of proliferative (cyclin D1 and c-myc) and antiapoptotic proteins (Mcl-1, Bcl-xL and survivin) in prostate cancer cells culminated in the induction of apoptosis, inhibition of DNA synthesis and cell growth, altered membrane integrity, marked reduction of invasiveness, inhibition of anchorage-dependent and -independent colony formation. Our data demonstrated for the first time that deguelin inhibits the growth and survival of human androgen-independent prostate cancer cells, and its anticancer and antimetastatic activity occurs, at least in part through downregulating GSK-3β/β-catenin signaling pathway and antiapoptotic survival proteins. Taken together our study indicates that deguelin may have translational potential as therapeutic agent for advanced or metastatic prostate cancer.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms