In vitro studies (animal cell lines)
The modulation of cell proliferation and apoptosis in mouse skin carcinoma cells (CH72) and non-tumourigenic epidermal cells (C50) have been studied in ethanol extracts from four species of mushroom fruiting bodies, mushroom spores and mushroom cultured broth. While extracts from mycelia of Grifola frondosa, Ganoderma lucidum, Hericium erinaceus, or from spores of G. lucidum exerted little, if any, effect on proliferation, the ethanol-soluble extract of Lentinula edodes (L.edodes, Shiitake) significantly decreased cell proliferation of CH72 cells. There were no changes in the proliferative response of the non-tumourigenic keratinocyte cell line, C50, to any of the mushroom extracts tested. L. edodes reduced cell proliferation and induced apoptosis in a time- and dose-dependent manner in carcinoma cells but had no effect in non-tumourigenic cells (C50). Cell cycle analysis demonstrated that the L.edodes extract induced a transient G1 arrest, with no change in the non-tumourigenic cells (Gu and Belury, 2005).
The cultivated mycelium of Cordyceps sinensis showed a significant and dose-dependent inhibitory effect on the proliferation of B16 mouse melanoma in C57BL/6 mice, causing a 60% decrease of tumour size over 27 days (Wu et al., 2007b).
In vitro treatment of cells with a methanol extract of Coriolus versicolor reduced melanoma cell viability in a dose-dependent manner. In the presence of the methanol extract, the proliferation of B16 cells was arrested in the G0/G1 phase of the cell cycle, followed by both apoptotic and secondary necrotic cell death. In vivo methanol extract treatment inhibited tumour growth in C57BL/6 mice inoculated with syngeneic B16 tumor cells. Peritoneal macrophages collected 21 days after tumour implantation from methanol extract-treated animals exerted stronger tumouristatic activity ex vivo than macrophages from control melanoma-bearing mice. Taken together, the results indicate that C.versicolor exerts anti-melanoma activity, both directly through anti-proliferative and cytotoxic effects on tumour cells and indirectly through promotion of macrophage anti-tumour activity (Harhaji et al., 2008).
Animal model (mouse) studies
Proflamin, isolated from the culture mycelium of Flammulina velutipes (Curt. ex Fr.) Sing. is a weakly acidic glycoprotein containing more than 90% protein and less than 10% carbohydrate, and has a molecular weight of ~13,000 Da. Proflamin has been shown to be markedly effective against the syngeneic tumours, B-16 melanoma (B-16) and adenocarcinoma 755 (Ca-755) in the mouse. The increases in median survival time of treated mice with B-16 and Ca-755 were 86% and 84%, respectively. Proflamin exhibited no cytocidal effect against the cultured cell lines in vitro. Oral administration of proflamin produced no lethal or any other apparent adverse effect in mice (Ikekawa et al., 1985).
An acidic polysaccharide from Phellinus linteus has been shown to markedly inhibit melanoma cell metastasis in mice, and directly inhibit cancer cell adhesion to, and invasion through, the extracellular matrix, but it had no direct effect on cancer cell growth. In addition, the authors reported that PL increased macrophage NO production. These results suggest that Phellinus linteus has two anti-metastatic functions - it acts as an immuno-potentiator and as a direct inhibitor of cancer cell adhesion (Han et al., 2006).
An extract of Ganoderma lucidum has also been reported to reduce chemically-induced mammary adenocarcinomas in Sprague Dawley rats and skin tumours Balb/c mice (Lakshmi et al., 2009). Mushroom oligosaccharides that down-regulate production of immuno-suppressive cytokines by ultraviolet radiation injured keratinocytes appear to be promising agents for the prevention of environmental (sun induced) skin cancer (Pelley and Strickland, 2000).