The anti-cancer effects of the medicinal mushroom Ganoderma lucidum (Reishi) were tested as a potential therapeutic for Inflammatory Breast Cancer (IBC). IBC is a rare, lethal and aggressive form of locally advanced breast cancer that manifests itself without a typical tumor mass. Studies suggest that the mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth via the regulation of protein synthesis. The mTOR effectors for protein synthesis are eukaryotic initiation factor 4E-binding protein 1 (4EBP-1) and the ribosomal protein S6 kinase (p70S6K). The 4EBP-eIF4E complex exerts control over cap-dependent translation, while p70S6K stimulates eIF4F translation of specific mRNAs with highly structured 5′UTRs, promoting cell growth, and tumor progression. In IBC the eukaryotic initiation factor, eIF4GI is overexpressed, which reprograms protein synthesis for cap-independent translation via increased initiation of internal ribosome entry site (IRES)-dependent translation. eIF4GI increased mRNA translation is partly responsible for the unique IBC pathological properties: overexpression of E-cadherin, strong homotypic IBC cell interaction, and formation of tumor emboli to promote IBC cell invasion. Using the patient derived IBC cell line, SUM 149, we previously demonstrated that Reishi extract selectively inhibits IBC cell growth and invasion by downregulating the expression of genes involved in invasion, survival and proliferation, and the protein expression of E-cadherin. The present study demonstrates that Reishi extract reduces the expression of AKT, which signals to activate the translational machinery by mTOR. Reishi extract reduced the expression of p70s6K and eIF4G, and diminished the expression of the IRES dependent mRNA containing proteins: c-Myc, p120 catenin, vascular endothelial growth factor (VEGF), BCL-2 and BCL-XL. Furthermore, Reishi extract reduced the expression of eIF4E and the phosphorylation of its inhibitor, 4EBP-1. Our results provide evidence that Reishi suppresses protein synthesis potentially by both cap-dependent and cap independent mechanisms. Our findings suggest that Reishi is a potential natural therapeutic that can be used in combination with traditional therapy to treat this intractable and deadly disease.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4228. doi:10.1158/1538-7445.AM2011-4228