Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population

Sze-Ue Luk,Terence Kin-Wah Lee,Davy Tak-Wing Lee,Franky Leung Chan,Stephanie Ma,Ming-Tat Ling,Irene Oi-Lin Ng,Yung-Tuen Chiu,Ji Liu,Yong-Chuan Wong,Kelvin Yuen Kwong Chan

doi:10.1371/journal.pone.0019804

Sze-Ue Luk, Terence Kin-Wah Lee + Show 9 more

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https://doi.org/10.1371/journal.pone.0019804

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Abstract

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

Highlights

Prostate cancer (PCa) is the most common male malignancy in western countries and represents a major disease burden in the world
To test if the anti-cancer effect of PSP is through targeting of cancer stem/progenitor cells (CSC) properties, we first investigated if PSP treatment affects the expression of prostate CSC markers in PC-3 cell line, which has been reported to contain CSCs
CSCs have been identified in prostate cancer cell lines such as LNCaP [26], DU145 [26,27] and PC-3 [28,29]

Summary

Introduction

Prostate cancer (PCa) is the most common male malignancy in western countries and represents a major disease burden in the world. The majority of PCa patients eventually relapse and develop hormone refractory PCa (HRPC), a fatal and terminal stage regarded as incurable [1]. Chemoprevention is an ideal strategy for battling prostate cancer, and a number of chemotherapeutic agents or natural food supplements are currently being tested for their potential of inhibiting prostate cancer development. Dutasteride, an analog of finasteride, was reported to significantly inhibit prostate cancer development [3]. Despite of the promising result, the side-effects associated with the finasteride treatment remains the major concern for it to be used widely for prostate chemoprevention. Bioactive food compounds such as epigallocatechin-3-gallate or resveratrol [4,5,6] represents an attractive alternative for prostate cancer chemoprevention, mainly due to their relatively low toxicity. Most of the previous studies have produced inconclusive results regarding their chemopreventive potential

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