Suppressive Effect and Molecular Mechanism of Houttuynia cordata Thunb. Extract against Prostate Carcinogenesis and Castration-Resistant Prostate Cancer.

Houttuynia cordata Thunb. (HCT) is a well-known Asian medicinal plant with biological activities used in the treatment of many diseases including cancer. This study investigated the effects of HCT extract and its ethyl acetate fraction (EA) on prostate carcinogenesis and castration-resistant prostate cancer (CRPC). HCT and EA induced apoptosis in androgen-sensitive prostate cancer cells (LNCaP) and CRPC cells (PCai1) through activation of caspases, down-regulation of androgen receptor, and inactivation of AKT/ERK/MAPK signaling. Rutin was found to be a major component in HCT (44.00 ± 5.61 mg/g) and EA (81.34 ± 5.21 mg/g) in a previous study. Rutin had similar effects to HCT/EA on LNCaP cells and was considered to be one of the active compounds. Moreover, HCT/EA inhibited cell migration and epithelial-mesenchymal transition phenotypes via STAT3/Snail/Twist pathways in LNCaP cells. The consumption of 1% HCT-mixed diet significantly decreased the incidence of adenocarcinoma in the lateral prostate lobe of the Transgenic rat for adenocarcinoma of prostate model. Similarly, tumor growth of PCai1 xenografts was significantly suppressed by 1% HCT treatment. HCT also induced caspase-dependent apoptosis via AKT inactivation in both in vivo models. Together, the results of in vitro and in vivo studies indicate that HCT has inhibitory effects against prostate carcinogenesis and CRPC. This plant therefore should receive more attention as a source for the future development of non-toxic chemopreventive agents against various cancers.

Hexane Insoluble Fraction from Purple Rice Extract Retards Carcinogenesis and Castration-Resistant Cancer Growth of Prostate Through Suppression of Androgen Receptor Mediated Cell Proliferation and Metabolism.

Prostate cancer and castration-resistant prostate cancer (CRPC) remain major health challenges in men. In this study, the inhibitory effects of a hexane insoluble fraction from a purple rice ethanolic extract (PRE-HIF) on prostate carcinogenesis and CRPC were investigated both in vivo and in vitro. In the Transgenic Rat for Adenocarcinoma of Prostate (TRAP) model, 1% PRE-HIF mixed diet-fed rats showed a significantly higher percentage of low-grade prostatic intraepithelial neoplasia and obvious reduction in the incidence of adenocarcinoma in the lateral lobes of the prostate. Additionally, 1% PRE-HIF supplied diet significantly suppressed the tumor growth in a rat CRPC xenograft model of PCai1 cells. In LNCaP and PCai1 cells, PRE-HIF treatment suppressed cell proliferation and induced G0/G1 cell-cycle arrest. Furthermore, androgen receptor (AR), cyclin D1, cdk4, and fatty acid synthase expression were down-regulated while attenuation of p38 mitogen-activated protein kinase, and AMP-activated protein kinase α activation occurred in PRE-HIF treated prostate cancer cells, rat prostate tissues, and CRPC tumors. Due to consistent results with PRE-HIF in PCai1 cells, cyanidin-3-glucoside was characterized as the active compound. Altogether, we surmise that PRE-HIF blocks the development of prostate cancer and CRPC through the inhibition of cell proliferation and metabolic pathways.

Attenuation of benign prostatic hyperplasia by hydrophilic active compounds from pigmented rice in a testosterone implanted rat model.

Benign prostatic hyperplasia (BPH) is a common chronic disease in aging men. The present study aimed to identify the active fraction of a purple rice extract and determine its anti-prostatic hyperplasia effect in a testosterone implanted rat model. The hexane insoluble fraction (HIF) which mainly contains hydrophilic phytochemicals from the purple rice crude ethanolic extract was defined as the active fraction, due to a potent effect on the downregulation of androgen receptor (AR) expression in malignant prostate cells, in addition to low toxicity for normal fibroblast cells. To induce BPH, subcutaneous implanting of a testosterone containing tube was performed in the castrated rats. Oral administration of HIF of at least 0.1 g kg-1 retarded prostate enlargement and improved histological changes induced by testosterone, without any effects on the serum testosterone levels. A lower proliferating cell nuclear antigen (PCNA) labelling index and the downregulated expression of AR, cyclinD1, and fatty acid synthase were clearly observed in the prostates of HIF-fed rats. Additionally, the mRNA levels of inflammation-related cytokines and enzymes in the prostate tissues significantly decreased after HIF treatment. Taken together, these findings demonstrate molecular mechanisms underlying the potential protective effects of the purple rice active fraction against testosterone-induced BPH in rats.

Purple rice extract inhibits testosterone-induced rat prostatic hyperplasia and growth of human prostate cancer cell line by reduction of androgen receptor activation.

The preventive effects of purple rice crude ethanolic extract (PRE) were firstly investigated on testosterone-induced benign prostatic hyperplasia (BPH) in castrated rats. As compared to vehicle-treated rats, lower prostate weights were found in the BPH rats that received PRE 1 g/kg bw. In addition, the PRE treatment down-regulated the androgen receptor (AR) expression in the dorsolateral prostate of those rats. In human prostate cancer cell line, LNCaP, PRE could reduce the cell growth, down-regulate the expression of AR and suppress prostate-specific antigen (PSA) secretion. Moreover, PRE also inhibited an activity of 5α-reductase from rat liver microsomes and the mutagenicity of Salmonella Typhimurium induced by standard mutagen. These results demonstrate that PRE altered testosterone-induced BPH in rats and retarded prostate cancer cell growth by modulating AR expression. It is therefore recommended that further investigation is undertaken into the chemopreventive potential of PRE in androgen-AR mediated diseases. PRACTICAL APPLICATIONS: This study revealed the mechanisms of purple rice extract on testosterone-induced rat benign prostatic hyperplasia. Such information, purple rice components show promise as an effective chemopreventive agent for prostatic hyperplasia prevention by alternating the influence of testosterone through its receptor. Thus, purple rice might be developed as food supplement for reduction of prostatic hyperplasia or cancer in elder men.