Rabbit Anti-Human TNFRSF6B Polyclonal antibody

Diarylpentanoid [l,5-bis(2-hydroxyphenyl)-l,4-pentadiene-3-one] (MS17) demonstrated enhanced anticancer activity compared to curcumin but its effect on androgen-independent prostate cancer has not been well-studied. The present study was aimed to perform gene expression profiling on MS 17 treated PC-3 and DU 145 cells using microarray technology to identify mutually regulated genes as common targets in both androgen-independent prostate cancer cell lines as well as molecular pathways that contributes to the anticancer activity of MS17. The profiling data revealed a dose-dependent gene regulation, evident by higher fold change expression values when the treatment dose was increased by 15-fold in both cell lines. Gene ontology classification was performed on highly regulated differentially expressed genes (DEGs). Among these genes, the mutually regulated DEGs were identified as common targets in both cell lines. The mutually up-regulated DEGs included, CRYAB and DNAI2 associated with cytoskeletal organization, HSPA6 and HSPB8 with response to unfolded protein, MMP3 and MMP10 with proteolysis, CACNA1G with transporter activity, NGFR with apoptosis, CCL26 with immune response, DNAJA4 with protein folding and TRIML2 with protein ubiquitination. However, the down-regulated genes such as CTDSP1 were associated with phosphatase activity, HIST1H2BFand HIST1H2AI with chromosome organization, MXD3 with regulation of transcription and TNFRSF6B with apoptosis. PC-3 and DU145 are androgen-independent prostate cancer cells with different biological properties, and identification of common targets in both cell lines could potentially be used as therapeutic targets. Pathway analysis of the DEGs in PC-3 cells demonstrated modulation of top pathways associated with cell cycle checkpoint, DNA damage, and inflammatory response while in DU145 cells the pathways were associated with immune response and metabolism. Thus, the findings of the present study provide insight into the antitumor activity of MS17 and as a potential chemotherapeutic agent for androgen independent prostate cancer cells.

Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin beta receptor (LT beta R, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LT beta R/HVEM pathway was associated with delayed downregulation of interleukin-7R alpha and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LT beta R/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.