Ethyl Gallate: Promising Cytoprotective against HIV-1-Induced Cytopathy and Antiretroviral-Induced Cytotoxicity.

Introduction: HIV-1 infection in cell culture is typically characterized by certain cytopathic effects such as vacuolization of cells and development of syncytia, which further lead to cell death. In addition, the majority of drugs during HIV treatment exhibit serious adverse effects in patients, apart from their beneficial role. During the screening of cytoprotective agents to protect the cells from HIV-1-associated cell death and also drug-associated toxicity, antioxidants from a natural source are assumed to be a choice. A well-known antioxidant, ethyl gallate (EG), was selected for cytoprotection studies which have already been proven as an anti-HIV agent. Objective: The main objective of the study was to explore the cytoprotective potential of EG against HIV-1-induced cytopathic effect and antiretroviral drug toxicity. Methods: DPPH free radical scavenging assay was performed with EG to find the effective concentration for antioxidant activity. HIV-1infection-associated cytopathic effects and further rescue by EG were studied in MT-2 lymphocytes by the microscopic method and XTT cytopathic assays. The cellular toxicity of different antiretroviral drugs in different cell lines and the consequent cytoprotective effectiveness of EG were investigated using an MTT cell viability assay. Results: Like ascorbic acid, EG exhibited promising antioxidant activity. HIV-1 infection of MT2 cells induces cell death often referred to as the cytopathic effect. In addition, the usage of antiretroviral drugs also causes severe adverse effects like cytotoxicity. In this context, EG was tested for its cytoprotective properties against HIV-1-induced cytopathic effect and drug-mediated cellular toxicity. EG reclaimed back the MT2 cells from HIV-1-induced cell death. Antiretroviral drugs, such as ritonavir, efavirinz, AZT, and nevirapine, were tested for their toxicity and induced more cell death at higher concentrations in different tissue models such as the liver (THLE-3), lung (AEpiCM), colorectal (HT-29), and brain (U87 MG). Pretreated cells with EG were rescued from the toxic doses of ART. Conclusion: EG was found to be exhibited cytoprotection not only from HIV-1-linked cell death but also from the chemotoxicity of antiretroviral drugs. Evidently, EG could be a cytoprotective supplement in the management of AIDS along with its enormous antioxidant benefits.

In vitro anti-HIV-1 activity of ethyl gallate.

In recent years, the exploration for potential inhibitors of HIV has been increased due to the development of drug resistant HIV strains in infected people undergoing antiretroviral agents treatment. In this report, we studied the anti-HIV properties of ethyl gallate (EG) against a panel of HIV-1 strains in in vitro conditions. Different clinical isolates and laboratory strains of HIV-1 were tested for their sensitivity with EG. We found that EG exhibited non-toxic nature over a wide range of cell lines from different tissue origin. Serum proteins have little to no impact on the antiviral activity of EG. In the present study, EG was found to be a promising anti-HIV agent.

ARID1B, a member of the human SWI/SNF chromatin remodeling complex, exhibits tumour-suppressor activities in pancreatic cancer cell lines.

BACKGROUND: The human ATP-dependent SWItch/sucrose nonfermentable (SWI/SNF) complex functions as a primary chromatin remodeler during ontogeny, as well as in adult life. Several components of the complex have been suggested to function as important regulators of tumorigenesis in various cancers. In the current study, we have characterised a possible tumour suppressor role for the largest subunit of the complex, namely the AT-rich interaction domain 1B (ARID1B). METHODS: We performed Azacytidine and Trichostatin A treatments, followed by bisulphite sequencing to determine the possible DNA methylation-induced transcription repression of the gene in pancreatic cancer (PaCa) cell lines. Functional characterisation of effect of ARID1B ectopic expression in MiaPaCa2 PaCa cell line, which harboured ARID1B homozygous deletion, was carried out. Finally, we evaluated ARID1B protein expression in pancreatic tumour samples using immunohistochemistry on a tissue microarray. RESULTS: ARID1B was transcriptionally repressed due to promoter hypermethylation, and ectopic expression severely compromised the ability of MiaPaCa2 cells to form colonies in liquid culture and soft agar. In addition, ARID1B exhibited significantly reduced/loss of expression in PaCa tissue, especially in samples from advanced-stage tumours, when compared with normal pancreas. CONCLUSION: The results therefore suggest a possible tumour-suppressor function for ARID1B in PaCa, thus adding to the growing list of SWI/SNF components with a similar function. Given the urgent need to design efficient targeted therapies for PaCa, our study assumes significance.