{
   "source_x": "PMC",
   "title": "Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid",
   "doi": "http://dx.doi.org/10.1002/jcb.24946",
   "pmcid": "PMC5012903",
   "abstract": "Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A\u2019s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma.",
   "authors": [
      "['Radwan, Faisal F. Y.', 'Hossain, Azim', 'God, Jason M.', 'Leaphart, Nathan', 'Elvington, Michelle', 'Nagarkatti, Mitzi', 'Tomlinson, Stephen', 'Haque, Azizul']"
   ],
   "id": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012903"
}