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. 2008 Dec;33(6):1307-13.

Pleurotus Ostreatus Inhibits Proliferation of Human Breast and Colon Cancer Cells Through p53-dependent as Well as p53-independent Pathway

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Pleurotus Ostreatus Inhibits Proliferation of Human Breast and Colon Cancer Cells Through p53-dependent as Well as p53-independent Pathway

Andrej Jedinak et al. Int J Oncol. .
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Abstract

In spite of the global consumption of mushrooms, only two epidemiological studies demonstrated an inverse correlation between mushroom intake and the risk of cancer. Therefore, in the present study we evaluated whether extracts from edible mushrooms Agaricus bisporus (portabella), Flammulina velutipes (enoki), Lentinula edodes (shiitake) and Pleurotus ostreatus (oyster) affect the growth of breast and colon cancer cells. Here, we identified as the most potent, P. ostreatus (oyster mushroom) which suppressed proliferation of breast cancer (MCF-7, MDA-MB-231) and colon cancer (HT-29, HCT-116) cells, without affecting proliferation of epithelial mammary MCF-10A and normal colon FHC cells. Flow cytometry revealed that the inhibition of cell proliferation by P. ostreatus was associated with the cell cycle arrest at G0/G1 phase in MCF-7 and HT-29 cells. Moreover, P. ostreatus induced the expression of the tumor suppressor p53 and cyclin-dependent kinase inhibitor p21(CIP1/WAF1), whereas inhibited the phosphorylation of retinoblastoma Rb protein in MCF-7 cells. In addition, P. ostreatus also up-regulated expression of p21 and inhibited Rb phosphorylation in HT-29 cells, suggesting that that P. ostreatus suppresses the proliferation of breast and colon cancer cells via p53-dependent as well as p53-independent pathway. In conclusion, our results indicated that the edible oyster mushroom has potential therapeutic/preventive effects on breast and colon cancer.

Figures

Figure 1
Figure 1
Effects of edible mushrooms on the proliferation of breast cancer and colon cancer cells. (A) MCF-7 and (B) HT-29 cells were treated for 24 h with 1 mg/ml of mushroom extract and proliferation was assessed as described in Materials and methods. Data are the mean ± SD of triplicate determinations. C, Control; AB, Agaricus bisporous; LE, Lentinus edodes; FV, Flammulina velutipes and PO, Pleurotus ostreatus.
Figure 2
Figure 2
Effects of P. ostreatus on the proliferation of breast cancer and mammary epithelial cells. (A) MDA-MB-231, (B) MCF-7, (C) MCF-10A cells were treated with P. ostreatus (0–1.0 mg/ml) for 24 and 48 h. Proliferation was assessed as described in Materials and methods. Data are the mean ± SD of triplicate determinations. Similar results were received in at least two additional experiments.
Figure 3
Figure 3
Effects of P. ostreatus on the proliferation of colon cancer and normal colon cells. (A) HCT-116, (B) HT-29, (C) FHC cells were treated with P. ostreatus (0–1.0 mg/ml) for 24 and 48 h. Proliferation was assessed as described in Materials and methods. Data are the mean ± SD of triplicate determinations. Similar results were received in at least two additional experiments.
Figure 4
Figure 4
P. ostreatus induces morphological changes in cancer cells. MCF-7 and HT-29 cells were treated with P. ostreatus (0; 1.0 mg/ml) for 48 h and morphological changes evaluated as described in Materials and methods.
Figure 5
Figure 5
P. ostreatus induces cell cycle arrest at G0/G1 phase. (A) MCF-7, (B) HT-29 cells were treated with P. ostreatus (1.0 mg/ml) for 0, 24 and 48 h, and cell cycle distribution was evaluated by flow cytometry as described in Materials and methods. Data are the mean ± SD of triplicate determinations.
Figure 6
Figure 6
Effects of P. ostreatus on cell cycle regulatory proteins. (A) MCF-7 cells and (B) HT-29 cells were treated with P. ostreatus (0–1.0 mg/ml) for 24 h. The expression of p21, p53, PCNA, Rb and pRb was evaluated in whole cell extracts by Western blot analysis with the respective antibodies. The equivalent amount of protein was verified by reprobing the blot with anti-β-actin antibody. The results are representative of three separate experiments. The expression level of p21 (ratio p21/β-actin) was quantified by densitometry as described in Materials and methods.
Figure 7
Figure 7
Schematic representation of the expression of cell cycle regulatory genes modulated by P. ostreatus in MCF-7 and HT-29 cells.

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