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 (GI50) 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 (IC50) 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.
Highlights
Nonsteroidal, plant-derived compounds that disrupt or mimic the normal action of estradiol are referred to as phytoestrogens
Given the high incidence of prostate cancer, there is an urgent need for treatment paradigms that improve prostate health
Nonsteroidal compounds are an interesting target for prostate cancer treatment because they do not produce the undesirable effects associated with traditional steroidal regimes [12, 39, 41, 42]
Summary
Nonsteroidal, plant-derived compounds that disrupt or mimic the normal action of estradiol are referred to as phytoestrogens. Organ culture studies showed that the phytoestrogen genistein decreased growth of prostate cancer tissue and benign prostatic hypertrophy [14,15,16]. Taken together, these studies suggest that some constituent of phytoestrogen-containing diets possesses antiandrogenic and antitumorogenic activities, which could provide some beneficial effects in prostate cancer patients [17]. Given the hormonal dependency of some of these biological activities, it is possible that nonsteroidal androgen present in Bizzy nut extracts be responsible for the medicinal value attributed to it. We describe the ability of a Bizzy nut extract to induce apoptosis in an AR-positive cell line and to modulate AR-dependent gene expression
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