Arabinogalactan G1-4A isolated from Tinospora cordifolia induces PKC/mTOR mediated direct activation of natural killer cells and through dendritic cell cross-talk.

Background: Tinospora cordifolia polysaccharide G1-4A activates antigen-presenting cells, but its effect on natural killer (NK) cells is not known. The objective of this study is to assess the effect of G1-4A on NK cells; direct effects as well as through dendritic cell (DC) cross-talk.

Methods: NK cell phenotype and function were assessed in spleen cells treated in vitro with G1-4A or isolated from mice administered with G1-4A.

Effects of prolonged treatment of TGF-βR inhibitor SB431542 on radiation-induced signaling in breast cancer cells.

Purpose: We have earlier characterized increased TGF-β signaling in radioresistant breast cancer cells. In this study, we wanted to determine the effect of prolonged treatment of TGF-βR inhibitor SB431542 on radiation-induced signaling, viz., genes regulating apoptosis, EMT, anti and pro-inflammatory cytokines.

COX-2 inhibitor prevents tumor induced down regulation of classical DC lineage specific transcription factor Zbtb46 resulting in immunocompetent DC and decreased tumor burden.

The interaction between the immune and tumor cells in the microenvironment is an important factor deciding the progression of cancer. Though many of the soluble mediators in the microenvironment that mediate immunosuppression are known, the mechanism by which the tumor affects the distal progenitors is not known. We report that the tumor derived prostanoids down regulated classical dendritic cells DC (cDC) lineage specific transcription factor Zbtb46 in the progenitor cells which affects its differentiation.

Potential Role of TRAIL in Metastasis of Mutant KRAS Expressing Lung Adenocarcinoma.

Apo2L/tumor necrosis factor (TNF)-α-related apoptosis-inducing ligand (TRAIL, TNFSF10) is an important cytokine in the tumor microenvironment and plays a major role in the balance of cell survival/death pathways. Bioinformatic analyses of 839 adenocarcinoma (AC) and 356 squamous cell lung carcinoma patient data (SCC) by cBioPortal (genomic analyses) shows that TRAIL expression leads to differential outcomes of disease free survival in AC and SCC. Oncomine datamining (transcript analyses) reveal that TRAIL is upregulated in 167 SCC as compared to 350 AC patients from six data sets.

Sulforaphane induces ROS mediated induction of NKG2D ligands in human cancer cell lines and enhances susceptibility to NK cell mediated lysis.

Aims: The goal of this study is to investigate the tumor cytotoxic effects of sulforaphane (SFN) and ionizing radiation (IR) as well as their ability to up-regulate natural killer group 2, member D (NKG2D) ligands and modulate the susceptibility of tumor cells to natural killer (NK) cell-mediated killing.

Main Methods: Expression of MHC class I-related chain molecules A and B (MICA/MICB) and total reactive oxygen species (ROS) were assessed by flow cytometry following labeling with appropriate dyes or antibodies. NK cell cytotoxicity was determined by calcein release of target cells.

G1-4A, a polysaccharide from Tinospora cordifolia induces peroxynitrite dependent killer dendritic cell (KDC) activity against tumor cells.

Dendritic cells (DC) play a central role in the development of an adaptive immune response against tumor. In addition to its role in antigen presentation, DC also possesses cytotoxic activity against tumor cells. We have earlier shown phenotypic and functional maturation of bone marrow derived dendritic cells (BMDC) by G1-4A, an arabinogalactan derived from Tinospora cordifolia.