Helicobacter pylori enhances HLA-C expression in the human gastric adenocarcinoma cells AGS and can protect them from the cytotoxicity of natural killer cells.

Helicobacter pylori (H. pylori) seems to play causative roles in gastric cancers. H. pylori has also been detected in established gastric cancers. How the presence of H. pylori modulates immune response to the cancer is unclear. The cytotoxicity of natural killer (NK) cells, toward infected or malignant cells, is controlled by the repertoire of activating and inhibitory receptors expressed on their surface. Here, we studied H. pylori-induced changes in the expression of ligands, of activating and inhibitory receptors of NK cells, in the gastric adenocarcinoma AGS cells, and their impacts on NK cell responses. AGS cells lacked or had low surface expression of the class I major histocompatibility complex (MHC-I) molecules HLA-E and HLA-C-ligands of the major NK cell inhibitory receptors NKG2A and killer-cell Ig-like receptor (KIR), respectively. However, AGS cells had high surface expression of ligands of activating receptors DNAM-1 and CD2, and of the adhesion molecules LFA-1. Consistently, AGS cells were sensitive to killing by NK cells despite the expression of inhibitory KIR on NK cells. Furthermore, H. pylori enhanced HLA-C surface expression on AGS cells. H. pylori infection enhanced HLA-C protein synthesis, which could explain H. pylori-induced HLA-C surface expression. H. pylori infection enhanced HLA-C surface expression also in the hepatoma Huh7 and HepG2 cells. Furthermore, H. pylori-induced HLA-C surface expression on AGS cells promoted inhibition of NK cells by KIR, and thereby protected AGS cells from NK cell cytotoxicity. These results suggest that H. pylori enhances HLA-C expression in host cells and protects them from the cytotoxic attack of NK cells expressing HLA-C-specific inhibitory receptors.

Novel peptide-based inhibitor for targeted inhibition of T cell function.

Novel immunosuppressants are sought to overcome the side effects of currently used drugs. T cells play a central role in the functioning of the immune system; hence, drugs that specifically inhibit T cell function are expected to be better immunosuppressants with fewer side effects than the ones currently used. Peptides that interfere with crucial protein-protein interactions (PPIs) have been shown to influence cell physiology and have therapeutic potential. In this study, we designed a peptide, GVITAA, which specifically inhibits the function of lymphocyte-specific protein kinase (LCK), a signaling molecule that is mainly expressed in T cells and is responsible for positively regulating T cell function. Aspartate Histidine -Histidine Cysteine (DHHC21) -LCK is an important PPI present in T cells; DHHC21 interacts with LCK and targets the kinase to membrane rafts by adding a palmitoyl group. GVITAA is a ten amino acid peptide that interferes with the DHHC21-LCK interaction, prevents the membrane localization of LCK, and inhibits LCK-mediated initiation of complex signal transduction pathways required for T cell activation. In this study, we present evidence that the GVITAA peptide when conjugated with a cell-penetrating peptide-human immunodeficiency virus transactivator of transcription (TAT) and incubated with mouse T cells specifically inhibits LCK-mediated T cell receptor signaling, cytokine secretion, and T cell proliferation. This peptide does not affect other non-T cell functions and is non-toxic. A similar strategy was also tested and demonstrated in human peripheral T cells.

Amberlite IR-120 (H) mediated "on water" synthesis of fluorescent Ruthenium(II)-arene 8-hydroxyquinoline complexes for cancer therapy and live cell imaging.

A series of Ruthenium-Quinolinol complexes (3a-d &4a-d) has been synthesized by employing a simple, efficient and environmental friendly condition. Catalytic role of Amberlite IRA-120(H) has been demonstrated. The structures of the new compounds were elucidated by the analysis of spectroscopic data. The stability of these complexes was measured by UV spectroscopy & time dependent NMR spectroscopy. These newly developed complexes were represented as potential anticancer agent against human breast carcinoma cell line (MCF-7), human Epitheloid Cervix Carcinoma (HeLa), human lung adenocarcinoma epithelial cell line (A549) and human colon cancer cell line (Caco-2). Most of the ruthenium complexes showed higher anticancer activity in MCF-7, HeLa and Caco-2 cell lines than cisplatin. A high selectivity (9-28 folds) was observed with these newly developed organoruthenium compounds in human cancer cell lines (MCF-7, HeLa and Caco-2) with respect to normal fibroblast cell line (MRC-5). Complex [(η6-hexamethylbenzene)RuCl(κ2-O,N-5-chloro-HyQ)]·Cl (4b), [(η6-hexamethylbenzene)RuCl(κ2-O,N-5,7-dibromo-HyQ)]·Cl (4c) and [(η6-hexamethylbenzene)RuCl(κ2-O,N-5-chloro-7-iodo-HyQ)]·Cl (4d) exhibited best cytotoxicity profiles in three reported human cancer cell lines (MCF-7, HeLa, Caco-2). Cellular imaging study was also performed with these newly developed organoruthenium compounds. Compound 4c might be utilized for cancer theranostic agents because of its significant quantum yield in water, high potency, selectivity and high cellular uptake in cancer cell lines.