Simultaneous and Dose XXXX Cytotoxic and Immune Stimulatory Activity of Betulin.

@entity10357 @entity137 @entity670 @entity5 @entity19 @entity2047 @entity6844 @entity98 @entity14939 @entity1990 @entity320
UNASSIGNED: Conventional cytostatic @entity5 treatments rarely result in the complete eradication of @entity5 cells. Therefore, new therapeutic strategies focus on antagonizing the immunosuppressive activity of established @entity5 . In particular, recent studies of antigen-loaded dendritic cells (DCs) eliciting a specific antitumor immune response has raised the hopes of achieving the complete elimination of @entity5 tissue. @entity670 , fingolimod and betulin have already been described as active compounds in different types of @entity5 . Herein, we applied an integrated screening approach to characterize both their cytostatic and their immune-modulating properties side-by-side. As will be described in detail, our data confirmed that all three compounds exerted proapoptotic and antiproliferative activity in different @entity6844 cell lines to a given extent, as revealed by an @entity98 assay, CFSE and @entity14939 staining. However, while @entity670 and fingolimod also affected the survival of primary bone marrow (BM) derived DCs of C57BL/6 @entity19 , betulin exhibited a lower @entity137 for BMDCs in comparison to the @entity320 cells. Moreover, we could show for the first time, that only betulin caused a simultaneous, highly specific immune-stimulating activity, as measured by the IL-12p70 release of @entity1990 -stimulated BMDCs by ELISA, which was due to increased @entity10357 mRNA expression. Interestingly, the activation of DCs resulted in enhanced T lymphocyte stimulation, indicated by increased @entity2047 and IFN-y production of cytotoxic T cells in spleen cell co-culture assays which led to a decreased viability of B16 cells in an antigen specific model system. This may overcome the immunosuppressive environment of a @entity5 and destroy @entity5 cells more effectively in vivo if the immune response is specific targeted against the @entity5 tissue by antigen-loaded dendritic cells. In summary, cytostatic agents, such as betulin, that simultaneously exhibit immune stimulatory activity may serve as lead compounds and hold great promise as a novel approach for an integrated @entity5 therapy.
