|KIM, SUNG-PHIL - Ajou University Of Korea|
|NAM, SEOK HYUN - Ajou University Of Korea|
Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2013
Publication Date: 5/13/2013
Citation: Kim, S., Nam, S., Friedman, M. 2013. Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-transplanted mice. Journal of Agricultural and Food Chemistry. 61:4898-1904.
Interpretive Summary: The progression (metastatic spread) of tumors from one organ to another is reported to be a major cause of poor clinical outcome in cancer patients. The edible medicinal Hericium erinaceus mushroom is called “Yamabushitake” in Japan or “Houtou” in China and is also known by the common name Lion’s Mane. In a previous study, we investigated the composition and antitumor effects of extracts in tumor-bearing mice. In a second study published in the Journal of Agricultural and Food Chemistry, Volume 60, pages 5590-5596, 2012, we found that administering the mushroom extacts to mice infected with a lethal dose of the virulent foodborne pathogen Salmonella Typhimurium protected them against liver damage and mortality via stimulation of the immune system. In this study, we have elucidate the mechanism of the observed inhibition of metastasis of cancer cells from one organ to another in terms several factors (biomarkers) known to be associated with the prevention of metastasis. The findings of the previous and present studies suggest that the whole mushroom or the two bioactive mushroom extracts have multiple benefits. They can protect mice against lethal infection with Salmonella Typhimurium via stimulation the immune system, reduce inflammation, and inhibit carcinogenesis and metastasis of cancer cells in vivo. These results indicate the H. erinaceus edible mushrooms are a multi-functional food that may have the ability to help prevent and/or treat infectious diseases and human cancers.
Technical Abstract: We investigated the anti-metastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of Hericium erinaceus strongly elicited cancer cell death through apoptosis, and inhibited metastasis of cancer cells to the lungs by 66% and 69%, respectively. HWE and MWE reduced the expression of matrix metalloproteinases MMP-2 and MMP-9 in cells and their activities in culture media. Urokinase-type plasminogen activator (u-PA), another extracellular matrix (ECM)-degrading proteinase, also showed decreased protein expression. In CT-26 cells, HWE and MWE down-regulated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylations. The reduced phosphorylations seem to cause reduction of activity of the MMPs, thereby blocking migration and invasion of cells. Dietary administration of HWE and MWE reduced the formation of tumor nodules in the lung by about 50% and 55%, respectively, and prevented increases in lung weight caused by cancer cell metastasis. These results demonstrate the effectiveness of HWE and MWE as beneficial anti-metastatic agents, targeting their upstream signaling molecules for mediating the expression of the ECM-degrading proteinases. Acidic and alkaline extracts were not bioactive. Bioactivity seems to be related to composition. H. erinaceus edible mushrooms have the potential to serve as a health-promoting functional food.