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Title:   Author  item
                                            KIM, SUNG-PHIL - Ajou University Of Koreaitem
                                            KANG, MI-YOUNG - Kyungpook National Universityitem
                                            KIM, JAE-HO - Ajou University Of Koreaitem
                                            NAM, SEOK-HYUN - Ajou University Of Koreaitem
                                            Friedman, Mendel
  Submitted to: Journal of Agricultural and Food Chemistry
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 1/16/2011
                                    Publication  Date: 9/28/2011
                                    Citation: Kim, S., Kang, M., Kim, J., Nam, S., Friedman, M. 2011. Composition and mechanism of anti-tumor effects of Hericium erinaceus mushroom extracts in tumor-bearing mice. Journal of Agricultural and Food Chemistry. 59(18):9861-9869.Interpretive Summary: Mushrooms are an important source of nourishment.  Phytochemicals in some edible/medicinal mushrooms are a potential source of bioactive safe compounds for cancer prevention and antimicrobial effects.  We related antitumor effects in mice of four mushroom fractions extracted with different solvents to their content of polysaccharides called ß-glucans determined by a commercial assay kit and the number of characterized compounds determined by mass spectrometry.  We found that daily intraperitoneal administration for two weeks of two Hericium erinaceus mushroom extracts with a high ß-glucan content to mice with transplanted tumors significantly reduced tumor size by about 40%.  Studies of the mechanism of the beneficial effects with the aid of chemical and cell assays showed that the regression of the tumors was accompanied by changes in several biomarkers associated with tumor cells.  The results indicate that the following three biomarkers play key roles in the molecular mechanism of tumor regression: activation of macrophages, induction of splenic natural killer (NK) cells, and inhibition of angiogenesis (blood flow to tumor cells).  These observations suggest that H. erinaceus mushrooms may have therapeutic potential against cancer.  Antimicrobial and anti-toxin effects of mushroom compounds against foodborne pathogens merit study.
                                Technical Abstract: We investigated anti-tumor effects of the following four extracts of freeze-dried Hericium erinaceus mushrooms in Balb/c mice intracutaneously transplanted on the backs with CT-26 colon cancer cells: HWE, hot-water extraction by boiling in water for 3 h; MWE, microwaving in 50% ethanol/water at 60 W for 3 min; ACE and AKE, boiling in 1% HCl or 3% NaOH for 2 h.  HWE and MWE with a higher content of ß-glucans, determined by an assay kit, than ACE and MKE were active in all bioassays.  GC/MS analyses showed the presence of 40, 27, 16, and 13 compounds, respectively, in the four extracts.  Daily intraperitoneal (ip) injections of HWE and MWE for 2 weeks significantly reduced tumor weights by 38% and 41%.  Tumor regressions were associated with changes in the following cancer biomarkers compared to phosphate buffer (PBS) treated control mice: 2.7- and 2.4-fold increases in cytolytic activity of splenic natural killer (NK) cells; restored NO production and phagocytosis in peritoneal macrophages to 70–74% and 95–98% of normal levels; ~2-fold increase in released pro-inflammatory cytokines TNF-a, IL-1ß, and IL-6 from macrophages; and ~56% and ~60% reductions in the number of blood vessels inside the tumor.  The pro-angiogenic factors VEGF, COX-2, and 5-LOX were also significantly reduced in mRNA and protein expression by tumor genes.  ELISA of tumor cells confirmed reduced expression of COX-2 and 5-LOX (32% and 31%).  Reduced COX-2 and 5-LOX expression down-regulated VEGF expression, resulting in inhibition of neo-angiogenesis inside the tumors.  The results indicate that induction of NK activity, activation of macrophages, and inhibition of angiogenesis all contribute to the mechanism of reduction of tumor size.


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