Ganoderma lucidum (Reishi) Inhibits Cancer Cell Growth and Expression of Key Molecules in Inflammatory Breast Cancer

Department of Biochemistry, Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico.
Nutrition and Cancer (Impact Factor: 2.32). 09/2011; 63(7):1085-94. DOI: 10.1080/01635581.2011.601845
Source: PubMed


Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells (SUM-149). Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E-cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase activity. These findings suggest that Reishi is an effective anti-IBC therapeutic.

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    • "Ganoderma lucidum (also known as Ling-Zhi or Reishi) is a medicinal mushroom that is widely appreciated as a traditional Chinese medicine throughout the world. It has been well documented that Reishi possesses a broad range of pharmacological properties including antitumor [1], immuno modulatory [2], and anti-inflammatory activities [3]. LZ-8 is an immunomodulatory protein that can be isolated from Reishi. "
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    ABSTRACT: - LZ-8, an immunomodulatory protein isolated from Ganoderma lucidum (also known as Ling-Zhi or Reishi), has been shown to promote cell proliferation and IL-2 production in T cells. In this study, we show that LZ-8 induces the expansion of both murine and human CD4(+) T cells into FOXP3(+) regulatory T (Treg) cells. LZ-8 treatment was found to stimulate a 4-fold and a 10-fold expansion in the Treg populations of murine and human primary CD4(+) T cells, respectively. In addition, the expression of CTLA-4 and IL-10 was induced in LZ-8-treated CD4(+) T cells. Using neutralizing antibodies and gene-deficient T-cell lines, we also found that LZ-8 promotes Treg expansion through a CD45-mediated signaling pathway and that the CD18-dependent induction of IL-2 was involved in Treg formation and IL-10 production. The suppressive activity of LZ-8 was confirmed using a murine model of DSS-induced colitis; the disease was alleviated by the adoptive transfer of LZ-8-treated CD4(+) T cells. In conclusion, a new regulatory function for LZ-8 was identified, and the molecular mechanisms underlying this function were elucidated.
    Full-text · Article · Jun 2013 · Evidence-based Complementary and Alternative Medicine
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    • "Using the established IBC cell model, SUM-149 cells, we previously published that Reishi selectively reduced cancer cell viability and invasion [9]. To test whether Reishi treatment affects the expression of genes specifically involved in the PI3K/AKT/mTOR pathway, we performed PI3K/AKT signaling RT2 Profiler PCR arrays in SUM-149 cells treated with vehicle or 0.5 mg/mL Reishi for 3 hours. "
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    ABSTRACT: The medicinal mushroom (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using and IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.
    Full-text · Article · Feb 2013 · PLoS ONE
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    ABSTRACT: Ganoderma lucidum extract (GL extract) shows potential antitumor and chemoprevention effects on three types of breast cancer: estrogen-receptor dependent, estrogen-receptor independent, and inflammatory. Such positive effects are primarily due to the bioactive constituents in the GL extract, triterpenes and polysaccharides. There seems to be a common GL extract anticancer mechanism at the molecular level for breast cancer and other types of cancers. Studies at cellular, molecular and genomic levels on the topic reveal the formulation of the molecular sequence of events in the GL extract antitumor mechanism. Such sequence facilitates the identification of GL extract antitumor molecular targets; such as Nuclear Factor Kappa Beta (NF-kB), a cancer promoter, a protein that acts as a switch to turn inflammation on and off in the body. Insights from studies of GL extract or its bioactive constituents on breast and other cancers, including practical applications, give rise to recommendations for how and when GL extract should be used, and what age group in the population may benefit the most from its use.
    No preview · Article · Nov 2011 · Current Topics in Nutraceutical Research
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