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.
ScienceDaily (May 24, 2011) — A mushroom used in Asia for its medicinal benefits has been found to be 100 percent effective in suppressing prostate tumour development in mice during early trials, new Queensland University of Technology (QUT) research shows.
The compound, polysaccharopeptide (PSP), which is extracted from the ‘turkey tail’ mushroom, was found to target prostate cancer stem cells and suppress tumour formation in mice, according to an article written by senior research fellow Dr Patrick Ling in the online journal PLoS ONE, published by the Public Library of Science.
Dr Ling, from the Australian Prostate Cancer Research Centre-Queensland and Institute for Biomedical Health & Innovation (IHBI) at QUT, said the results could be an important step towards fighting a disease that kills 3,000 Australian men a year.
“The findings are quite significant,” Dr Ling said.
“What we wanted to demonstrate was whether that compound could stop the development of prostate tumours in the first place.
“In the past, other inhibitors tested in research trials have been shown to be up to 70 percent effective, but we’re seeing 100 percent of this tumour prevented from developing with PSP.
“Importantly, we did not see any side effects from the treatment.”
Dr Ling said conventional therapies were only effective in targeting certain cancer cells, not cancer stem cells, which initiated cancer and caused the disease to progress.
During the research trial, which was done in collaboration with The University of Hong Kong and Provital Pty Ltd, transgenic mice that developed prostate tumours were fed PSP for 20 weeks.
Dr Ling said no tumours were found in any of the mice fed PSP, whereas mice not given the treatment developed prostate tumours. He said the research suggested that PSP treatment could completely inhibit prostate tumour formation.
“Our findings support that PSP may be a potent preventative agent against prostate cancer, possibly through targeting of the prostate cancer stem cell population,” he said.
He said PSP had been previously shown to possess anti-cancer properties, and ‘turkey tail’ mushrooms (known as Coriolus versicolor or Yun-zhi) had been widely used in Asia for medicinal benefits.
However, Dr Ling said it was the first time it had been demonstrated that PSP had anti-cancer stem cell effects.
Although ‘turkey tail’ mushrooms had valuable health properties, Dr Ling said it would not be possible to get the same benefit his research showed from simply eating them.
A fundraiser has been organised in September to support further tests for the therapeutic potential of PSP against prostate tumours either alone or in combination with other anti-cancer compounds.
The incidence of prostate cancer varies greatly throughout the world; it is highest in African-Americans and lowest in the Asian populations of China, India, and Japan. Geographical differences in both prevalence of latent prostate cancer and mortality have been postulated to be influenced by diverse tumor-promoting and protective factors, both environmental and dietary. Prostate cancer is a tumor with an extremely long latency; the pattern of prostate tumorigenesis, in terms of the display and sequence of appearance of particular molecular or biochemical features, or morphological changes, characterizing different stages of the carcinogenic process, is expected to be heterogeneous. Some insights into tumor heterogeneity and progression can be obtained from studies using cell lines, particularly those derived from different anatomical sites. The present study aims to investigate whether hormone-responsive LNCaP and androgen-refractory JCA-1, PC-3, and DU-145 prostate cancer cells are responsive to Yunzhi (YZ), a proprietary dietary supplement prepared from extracts of Trametes versicolor, also known as Coriolus versicolor (a mushroom consumed by Chinese for its purported health benefits), and to elucidate its mechanism of action. Ethanolic extracts (70%) of YZ significantly reduced LNCaP cell growth, down-regulated the levels of secreted PSA, but had less effects on the expression of intracellular PSA and did not affect levels of the androgen receptor. In androgen-unresponsive prostate cancer cells, YZ had a much less pronounced suppressive effect on proliferation of PC-3 and DU-145 cells, compared to LNCaP, and was inactive against JCA-1 cells. Western blot analyses show that the expression of Rb, a key regulatory protein in G1/S transition, and PCNA, integrally involved in mammalian cell DNA replication, were significantly reduced by treatment with YZ in PC-3 and DU-145 cells, respectively. In contradiction, none of these biochemical parameters were affected in JCA-1 cells under identical treatment conditions. Further analysis shows that YZ increased the levels of signal transducer and activator family of transcription factors STAT 1 and STAT 3 in JCA-1 and not LNCaP cells. The greater sensitivity of LNCaP cells to this polysaccharopeptide raises the possibility that YZ may be considered as an adjuvant therapy in the treatment of hormone responsive prostate cancer; additionally, it may have chemopreventive potential to restrict prostate tumorigenic progression from the hormone-dependent to the hormone-refractory state.