lucidum and these substances belong to the triterpenoids. triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both and 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 usually a candidate for future drug design for the treatment of lymphoma. (Fig. 1A), has the potential to play a dual-role in a chemo- and immunotherapeutic regimen of human B-cell lymphoma. Open in a separate windows Fig. 1 The chemical structure of the triterpenoid [Ganoderic acid A (GA-A)], and GA-As anti-proliferative activity in B-lymphoma cells. (A) GA-A chemical structure. (B) A pre-B acute lymphocytic leukemia line (NALM-6), Burkitts lymphoma (Ramos, CA-46 and GA-10), (C) non-Hodgkins lymphoma (DB and Toledo), (D) B-lymphoblastoid cell lines (6.16.DR4.DM, Frev and Priess), and (E) primary B-cells from lymphoma patients and healthy individuals were treated with GA-A (5C40M) Prostratin for 24h, followed by a cell viability assay as described in the methods section. Control cells treated with vehicle alone were utilized to calculate the percent anti-proliferative activity induced by GA-A as indicated. Primary B-cells obtained from lymphoma patients include follicular B-cell lymphoma (TB#2759), diffuse large B-cell lymphoma (TB#2952), and chronic lymphocytic leukemia (TB#3284). These cells were treated with vehicle alone or GA-A, and viable cells were counted using trypan blue dye exclusion. The percent cell viability as compared Prostratin to control was calculated as described in the methods. The data shown are results of at least three individual experiments performed in triplicate wells. Error bars represent mean S.D. Significant differences were indicated as (* 0.01), where ns indicates (not significant). has been used for centuries in Far East countries as a folk remedy for its antitumor and health promoting effects [Hsieh and Wu, 2011; Sliva, 2003]. Due to its presumed health benefits and apparent absence of side-effects, it has also been widely consumed as a dietary supplement by cancer patients [Hsieh and Wu, 2011]. The major constituents of include polysaccharides and triterpenes [Boh et al., 2007; Wubshet et al., 2012], and both components seem to have profound anti-proliferative activities [Chen et al., 2004; Kimura et al., 2002; Sadava et al., Rabbit Polyclonal to SHP-1 2009]. Ganoderic acids (GAs) are one of major compounds with potent pharmacological activity found in G. lucidum and these compounds belong to the triterpenoids. It is widely believed that GA possesses numerous properties including anti-oxidant, anticancer, antiviral, and anti-platelet aggregation properties. Although crude GAs and their derivatives have been tested in many occasions [Jiang et al., 2008; Li et al., 2012; Liu et al., 2012; Wu et al., 2012; Yao et al., 2012], purified GA-A has not been investigated in details. The molecular formula of GA-A is usually C30H44O7, and its approximate molecular mass is usually 516 daltons. This natural product may have a potential to play important functions in immune regulation and inhibition of leukemia and lymphoma growth. The affordability of GA-A may also provide windows of opportunity, such as its co-administration with traditional anticancer drugs for overcoming malignancy cell Prostratin resistance to chemotherapy. B-cell lymphoma arises in lymphoid organs due to unprecedented atypical proliferation of lymphoid cells, thus compromising immune function [Siegel et al., 2012]. The disease is regarded as a leading cause of new cancer cases in the United States. Recently, it has been estimated that leukemia and lymphoma accounts for 7.7% of new cancer cases and 7.6% of new cancer-related deaths in the US. B-cell lymphoma also occurs at any age, and the development and progression of this malignancy involves complex interactions between the neoplastic B-cells and the surrounding microenvironment, highlighting the need for a new therapeutic strategy. Recent studies suggest that myeloid-derived suppressor cells (MDSCs) represent a subset of antigen presenting cells which accumulate in tumor microenvironment and induce immune tolerance in malignancies [Goh et al., 2013; Kennedy et al., 2011; Khaled et al., 2013]. MDSCs are comprised of hematopoietic progenitor cells and precursors of macrophages, dendritic cells, and immature granulocytes. These cells are of great interest because they have the capacity to suppress the adaptive immune response mediated by.