A128

The beneficial effects of the individual compounds (anti-angiogenic, immunomodulatory polysaccharides and cytotoxic triterpenes) of the medicinal mushroom Ganoderma lucidum (Reishi) have been investigated and proven to be effective in the prevention of cancer. However, little information is known about the effects of whole mushroom Reishi extract as a dietary supplement and its potential of achieving a cumulative biological effect that exceeds those of fractionated compounds. In addition, the effects of Reishi extract have not been investigated in preventing Inflammatory Breast Cancer (IBC), the most lethal and least understood form of locally advanced breast cancer. IBC possesses a distinctive phenotype characterized by tumor emboli formation, lymphocytic infiltration, angiogenesis, and vasculogenesis. Furthermore, molecular studies demonstrate that genes involved in cell-cell adhesion (CHD1), angiogenesis and cell proliferation (VEGF, bFGF), cytokines (IL-6, IL-8), extracellular matrix rearrangement (RhoC), and the nuclear factor (NF)-kappaB, and its target genes are overexpressed in IBC. Therefore we hypothesized that the immunomodulatory, anti-inflammatory and anti-cancer effects of the compounds present in the Reishi extract may have preventive effects that diminish IBC progression. The effects of the dietary supplement were tested in vitro. Using the normal mammary epithelial cell line, MCF10A and the IBC cell line, SUM-149, treated with vehicle, or 0.25 mg/mL and 0.50 mg/mL of Reishi extract for 48 hr, we show that the dietary supplement is selectively effective in inhibiting cell proliferation of the IBC cell line SUM-149 but not in the normal mammary epithelial cell line MCF10A in a time-dependent manner. We also demonstrate that Reishi extract can inhibit SUM-149 cell invasion via a 3-D cell culture after 24 hr of treatment with 0.50 mg/mL of Reishi extract. Finally, as evidenced by RT2 profiler cancer pathway finder PCR arrays, our results indicate that treatment with vehicle or 0.50 mg/mL of Reishi extract for 8 hr significantly down-regulates the expression of genes that induce apoptosis, thus decrease cancer cell survival and that are involved in chromosome synthesis (BCL-2, CDKN2A, TERT). It also decreases the expression of genes involved in invasion, metastasis and tumor progression (MMP9), or mitogenesis, angiogenesis, cell proliferation and migration genes (PDGFB), and up-regulates the expression of cytokine genes (IL-8). A total of 52% of tumorigenesis genes were down-regulated in cells treated with the Reishi extract compared to those exposed to vehicle alone. Overall, these results demonstrate that Reishi extract, is effective in inhibiting IBC progression, and may be a potential dietary supplement to prevent this deadly disease.

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA