Slaton J, Sloper D, McKenna D, Taylor M, Wilson M.

Down regulation of matrix metalloproteases and tumor inhibition of Ganoderma Lucidum (Reishi) mushroom depends upon triterpene content.

University of Minnesota, 420 Delaware SE, Minneapolis, MN 55416. jwsuro@hotmail.com

PURPOSE: Triterpenes are known to be inhibitors of the matrix metalloproteases (MMP) which regulate cellular motility and invasion. We investigated whether triterpene content in mushroom extracts would impact the growth and metastasis of prostate cancer growing orthotopically in mice.

METHODS: The human prostate cancer cell line, PC3-LN4 was exposed to increasing doses of different subspecies of ganoderma lucidum (G.Lucidum, Reishi) which contain different levels of triterpenes. The effect of triterpene content on growth and migration were assessed, and expression and activity of differing MMPs was determined by RT-PCR and zymography, respectively.For the in vivo experiments, PC3-LN4 cells (2x10) were then injected into prostates of nude mice. After 3 days, oral therapy was begun with varying doses of a G. lucidum subspecies containing high levels of triterpenes (1-20 mg/kg). The mice were sacrificed on day 30 and tumor growth assessed. The prostates were weighed and then preserved in formalin or nitrogen.

RESULTS: Mushroom extracts with the highest triterpene content had he greatest inhibitory effect on in vitro growth of tumor cells and inhibited expression of MMP-2. The triterpene-containing G. lucidum inhibited growth and down-regulated MMP expression by the prostate tumor cells (2-3 fold) in a triterpene-content-dependent fashion. Oral therapy with the highest dose of G. lucidum with the greatest triterpene content results in a reduction in prostate weight (mean weight: 220 mg for saline control, 108 mg for 5 g/kg of extract, and 87 mg 20 g/kg of extract) and decreased the number of nodes containing metastatic tumor by 40%. Mice were then treated with 4 different subspecies of G. lucidum with triterpene content ranging from near zero to up to 7% for 30 days. The G. lucidum subspecies with the highest content had the greatest inhibitory effect on orthotopic tumor growth (2-fold reduction) compared to the subspecies with no triterpenes. There was a corresponding decrease in MMP expression in tumors sections.

CONCLUSIONS: These results demonstrate that triterpene content in mushroom extract has an impact on prostate cancer growth and metastasis. This triterpene-dependent effect may be due in part to its regulation of MMPs. Which triterpene is most critical to the anti-tumor efficacy of G. Lucidum extracts remains to be elucidated.

 

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