The current study was intended to evaluate the hepatoprotective effect of Epicatechin (EC) against radiation-induced oxidative stress, in terms of inflammation and lipid peroxidation. Swiss albino mice were administered with EC (15 mg/kg body weight) for three consecutive days before exposing them to a single dose of 5-Gy (60)Co gamma (γ) irradiation. Mice were necropsied and livers were taken for immunohistochemistry, western blot analysis and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were increased whereas the activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) content and ferric reducing antioxidant power (FRAP) were diminished upon radiation exposure compared to control. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited whereas an increase in SOD, CAT, GSH and FRAP was observed in the mice treated with EC prior to irradiation. Thus, pre-treatment with EC offers protection against γ-radiation induced hepatic alterations.

Polyurethane diol (PUR-diol), a synthetic polymer, is widely used as a modifier for water-soluble resins and emulsions in wood appliances and auto coatings. Non-biodegradability of polyurethanes (PUR) and PUR-based materials poses a threat to environment that has led scientists to isolate microbes capable of degrading PUR. However, the bio-degradation of PUR-diol has not yet been reported. In this study, we report isolation of a soil bacterium that can survive using PUR-diol as sole carbon source. PUR-diol degradation by the organism was confirmed by thin layer chromatographic analysis of the conditioned medium obtained after the growth wherein a significant reduction of PUR-diol was observed compared to non-inoculated medium. To quantify the PUR-diol degradation, a sensitive assay based on High Performance Thin Layer Chromatography has been developed that showed 32% degradation of PUR-diol by the organism in 10 days. Degradation kinetics showed the maximal depletion of PUR-diol during logarithmic growth of the organism indicating a direct relation between the growth and PUR-diol degradation. Mutagenic study and GC-MS analysis revealed that esterase activity is involved in this degradation event. The ribotyping and metabolic fingerprinting analysis showed that this organism is a strain of Pseudomonous aeruginosa (P. aeruginosa). It has also been observed that this strain is able to degrade Impranil DLN™, a variety of commercially available PUR. Therefore this study identifies a new bacterium from soil that has the potential to reduce PUR-related waste burden and adds a new facet to diverse functional activities of P. aeruginosa.

Colorectal cancer is one of the leading causes of cancer-related death worldwide. The adenomatous polyposis coli (APC) gene is mutated in hereditary colorectal tumors and in more than 80% of sporadic colorectal tumors. APC mutations impair β-catenin degradation, leading to its permanent stabilization and increased transcription of cancerdriving target genes. In colon cancer, impairment of β-catenin degradation leads to its cytoplasmic accumulation, nuclear translocation, and subsequent activation of tumor cell proliferation. Suppressing β-catenin signaling in cancer cells therefore appears to be a promising strategy for new anticancer strategies. Recently, we discovered a novel Vibrio cholerae cytotoxin, motility-associated killing factor A (MakA), that affects both invertebrate and vertebrate hosts. It promotes bacterial survival and proliferation in invertebrate predators but has unknown biological role(s) in mammalian hosts. Here, we report that MakA can cause lethality of tumor cells via induction of apoptosis. Interestingly, MakA exhibited potent cytotoxic activity, in particular against several tested cancer cell lines, while appearing less toxic toward nontransformed cells. MakA bound to the tumor cell surface became internalized into the endolysosomal compartment and induced leakage of endolysosomal membranes, causing cytosolic release of cathepsins and activation of proapoptotic proteins. In addition, MakA altered β-catenin integrity in colon cancer cells, partly through a caspase-and proteasome-dependent mechanism.Importantly, MakA inhibited β-catenin-mediated tumor cell proliferation. Remarkably, intratumor injection of MakA significantly reduced tumor development in a colon cancer murine solid tumor model. These data identify MakA as a novel candidate to be considered in new strategies for development of therapeutic agents against colon cancer.

Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.

Conventional anticancer therapies are effective but have side effects, so alternative targets are being developed. Bacterial toxins that can kill cells or alter the cellular processes like proliferation, apoptosis and differentiation have been reported for cancer treatment. In this study we have shown antitumor activity of hemagglutinin protease (HAP) secreted by Vibrio cholerae. One µg of HAP showed potent antitumor activity when injected into Ehrlich ascites carcinoma (EAC) tumors in Swiss albino mice. Weekly administration of this dose is able to significantly diminish a large tumor volume within 3 weeks and increases the survival rates of cancerous mice. HAP showed apoptotic activity on EAC and other malignant cells. Increased level of pro-apoptotic p53 with increased ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2 signify that HAP induced apoptogenic signals lead to death of the tumor cells. In vivo and ex vivo studies suggest that mitochondrial dependent intrinsic pathway is responsible for this apoptosis. The level of ROS in malignant cells is reported to be higher than the normal healthy cells. HAP induces oxidative stress and increases the level of ROS in malignant cells which is significantly higher than the normal healthy cells. As a result the malignant cells cross the threshold level of ROS for cell survival faster than normal healthy cells. This mechanism causes HAP mediated apoptosis in malignant cells, but normal cells remain unaltered in the same environment. Our study suggests that HAP may be used as a new candidate drug for cancer therapy.