Abstract
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.
Highlights
Prostate cancer is the second most common cancer in the older male population [1]
We firstly describe the protective effects of an anthocyanin-rich purple rice extract against prostate carcinogenesis and castration-resistant prostate cancer (CRPC) growth
The percentage of adenocarcinoma in the lateral prostates was significantly decreased in the 1% purple rice extract (PRE)-HIF-fed group (F (2, 30) = 2.748, p = 0.049)
Summary
The development of prostate cancer at an early-stage depends on the activity of androgens and explains why androgen deprivation therapy (ADT) is the primary treatment for patients with this cancer [2]. Bioactive compounds of purple rice, especially anthocyanins, possess various biological properties including antioxidant, anti-atherosclerotic, anti-inflammatory, as well as anti-tumor activities [6,7]. The suppressive effect of crude ethanolic purple rice extract (PRE) on testosterone-induced benign prostatic hyperplasia (BPH) in rats has been reported [8]. PRE-HIF contained anthocyanins, including cyanidin-3-glucoside (C3G) and peonidin-3-glucoside (P3G). PRE-HSF contained other antioxidant metabolites, such as vitamin D derivatives and γ-oryzanol but no anthocyanins. The anthocyanin-rich fraction, PRE-HIF, was identified as the highly active and non-toxic fraction of purple rice extract on the BPH setting [9]. We are interested in the purple rice anthocyanins as candidates of prostatic chemopreventive agents
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