title: Molecular and biochemical effects of a kola nut extract on androgen receptor-mediated pathways.
abstract: The low incidence of prostate cancer in Asians has been attributed to chemopreventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemopreventative properties of the Jamaican bush tea "Bizzy," using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI(50)) of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the proapoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC(50)) of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.
authors.affiliation: Department of Environmental Toxicology, Southern University and A&M College, P.O. Box 9264, 108 Fisher Hall, Baton Rouge, LA 70813, USA.
authors.forename: Rajasree
authors.initials: R
authors.lastname: Solipuram
authors.forename: Sowmya
authors.initials: S
authors.lastname: Koppula
authors.forename: Angela
authors.initials: A
authors.lastname: Hurst
authors.forename: Kinesha
authors.initials: K
authors.lastname: Harris
authors.forename: Srivatcha
authors.initials: S
authors.lastname: Naragoni
authors.forename: Krystal
authors.initials: K
authors.lastname: Fontenot
authors.forename: Wesley
authors.initials: W
authors.lastname: Gray