A Concentrated Aglycone Isoflavone Preparation (GCP) That Demonstrates Potent Anti-Prostate Cancer Activity In vitro and In vivo

Abstract

Purpose: Isoflavones have anticancer activities, but naturally occurring isoflavones are predominantly glycosylated and poorly absorbed. Genistein combined polysaccharide (GCP; Amino Up Chemical Co., Sapporo, Japan), is a fermentation product of soy extract and basidiomycetes mycillae that is enriched in biologically active aglycone isoflavones. This study analyzes GCP in vitro and in vivo for potential utility as a prostate cancer chemopreventative agent.Experimental Design: Androgen-sensitive LNCaP and androgen-independent PC-3 cells were grown with various concentrations of GCP. In vitro cell growth was analyzed by the WST-1 assay, and apoptosis was assessed by fluorescence-activated cell sorting and detection of poly(ADPribose) polymerase cleavage using Western blot techniques. Effects of GCP on expression of cell cycle-regulatory proteins p53 (LNCaP only), p21, and p27 and the protein kinase Akt were considered using Western blot techniques. An in vivo LNCaP xenograft model was used to study the effects of a 2% GCP-supplemented diet on tumor growth in comparison with a control diet.Results: GCP significantly suppressed LNCaP and PC-3 cell growth over 72 h (89% and 78% in LNCaP and PC-3, respectively, at 10 g/ml; P < 0.0001). This reduction was associated with apoptosis in LNCaP cells, but not in PC-3 cells. GCP induced p27 and p53 (LNCaP only) protein expression within 6 h and suppressed phosphorylated Akt in both cell lines. The 2% GCP-supplemented diet significantly slowed LNCaP tumor growth, increasing apoptosis (P < 0.001), and decreasing proliferation (P < 0.001) over 4 weeks.Conclusions: GCP has potent growth-inhibitory effects against prostate cancer cell lines in vitro and in vivo. These data suggest GCP has potential as an effective chemopreventive agent against prostate cancer cell growth.

Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model

“…15,[21][22][23][24] Feeding mice with soy phytochemical concentrate (SPC, containing genistein, daidzein and glycitein) or an aglycone isoflavone preparation reduced tumor growth of s.c. implanted human LNCaP cells in immunocompromised mice. 15,22 In a prevention study of Zhou et al, 23 using an orthotopic model of LNCaP cells in SCID mice similar to our model, SPC was more effective than genistein or soy protein. This prevention study is in agreement with the efficacy demonstrated by soy isoflavones in our therapeutic study of established prostate tumors.…”

Afzelin exhibits anti-cancer activity against androgen-sensitive LNCaP and androgen-independent PC-3 prostate cancer cells through the inhibition of LIM domain kinase 1

“…The cultures were prepared in quadruplicate for each afzelin concentration and time point, and maintained in a CO 2 incubator for three days. After 24, 48 and 72 h, 10 µl water soluble tetrazolium salt (WST)-1 labeling solution (WST-1 cell proliferation assay kit; Roche Diagnostics, Indianapolis, IN, USA) was added to the cultures and the cells were returned to the CO 2 incubator for 2 h (19). The specific type of formazan product formed was detected by measuring its absorbance in a 96-well spectrophotometric plate reader (DiaSorin, Stillwater, MN, USA) at a wavelength of 420 nm, as described by the manufacturer (20).…”

Inhibition of Akt pathways in the treatment of prostate cancer

“…In many different cell lines and xenografts, the tyrosine kinase inhibitory characteristics of genistein induce apoptosis, cell-cycle arrest, hinders proliferation, prevents angiogenesis, and blocks androgen and estrogen-stimulated transcription. [56][57][58][59][60] In addition, studies demonstrate genistein may oppose many cellular survival mechanisms induced by radiation, chemotherapy or androgen deprivation, suggesting the usefulness of this agent as adjunctive therapy. 61,62 Subsequent analysis of these favorable biochemical changes reveal that many of them are mediated through Akt pathways (see Figure 1).…”

“…Concentrated aglycone-rich food supplements, such as genistein combined polysaccharide (GCP), may allow higher plasma levels of isoflavones. 58 Recently, a prospective randomized study by Rannikko et al 65 found that prostate tissue concentrates phytoestrogens including genistein, thus suggesting that plasma concentrations underestimate tissue concentrations by over 50%.…”