BackgroundBreast cancer is the most common cancer which causes significant morbidity and mortality among women worldwide. Lack of medical facilities for early detection, therapeutic strategies for treatment and side effects due to pharmacological compounds have encompassed the need for new therapies mostly from natural sources. A lot of components have been identified from different snake venoms as therapeutic agents. A group of polypeptides (60–70 amino acid residues) called cytotoxins or cardiotoxins present in an elapid family of snakes have a wide variety of pharmaceutical actions and have the tendency to damage a wide variety of cells including cancerous cells. The aim of the present study was to evaluate the cytotoxic effect of NN-32 protein toxin purified from Indian Spectacled Cobra venom against human breast cancer cell lines (MCF-7 and MDA-MB-231).MethodsThe NN-32 toxin was purified by ion exchange chromatography and further by RP-HPLC. The potential anticancer effects of the NN-32 toxin on MCF-7 and MDA-MB-231 cells were evaluated using MTT, anti-proliferation, neutral red (NR) uptake and Lactate Dehydrogenase (LDH) release assay.ResultsThe ion exchange chromatography showed various peaks among fraction no. 35 showing cytotoxic activity and this fraction showed a single peak with retention time 3.6 mins by HPLC using C18 column. The NN-32 toxin induced cytotoxicity in MCF-7 and MDA-MB-231 cells with the IC50 value of 2.5 and 6.7 μg/ml respectively. The NN-32 showed significant cytotoxicity to both the cell lines along with low cytotoxicity to MCF-10A (normal breast epithelial) cells. The cytotoxic effect was further confirmed by the anti-proliferative, NR uptake and LDH release assays.ConclusionThe purified toxin NN-32 from Naja naja venom showed cytotoxic activity against MCF-7 (ER+) and MDA-MB-231(ER-) cells in both dose dependent and time dependent manner.
Background: Cancer is the second most common fatal disease in the world, behind cardiovascular disorders in the first place. It accounts for around 0.3 million deaths per year in India due to the lack of proper diagnostic facilities, prevention and treatment. Current therapeutic methods do not provide adequate protection and affect normal cells along with cancerous ones. Thus, there is a need for some alternative therapeutic strategy, preferably from natural products, which have been traditionally used for treatment of various diseases in the country. Methods: In this study, we have conjugated purified NN-32 toxin from Naja naja venom with gold nanoparticles and its anticancer potential was evaluated against human breast cancer cell lines. UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy and zeta potential analysis were the techniques used for characterization of GNP-NN-32. Results: GNP-NN-32 showed dose-and time-dependent cytotoxicity against breast cancer cell lines (MCF-7 and MDA-MB-231). NN-32 and GNP-NN-32 induced apoptosis in both breast cancer cell lines. The results of CFSE cell proliferation study revealed that NN-32 and GNP-NN-32 arrested cell division in both MCF-7 and MDA-MB-231 cell lines resulting in inhibition of proliferation of these cancer cells. Conclusion: GNP-NN-32 showed an anticancer potential against human breast cancer cell lines. Analysis of detailed chemical characterization along with its cytotoxic property might help to perceive a new dimension of the anti-cancer potential of GNP-NN-32 that will enhance its biomedical function in near future.
Background: NN-32 toxin which was obtained from Naja naja venom and showed cytotoxicity on cancer cell lines. As the toxicity of NN-32 is the main hurdle in the process of drug development; hence, we have conjugated NN-32 toxin with gold nanoparticles (GNP-NN-32) in order to decrease the toxicity of NN-32 without reducing its efficacy, GNP-NN-32alleviated the toxicity of NN-32 in invitro studies during the course of earlier studies. In continuation, we are evaluating in vivo toxicity profile of NN-32 and GNP-NN-32 in the present study. Objective: To study in vivo toxicity profile of NN-32 and nanogold conjugated GNP-NN-32 from Naja naja venom. Materials and Methods: We have carried out in vivo acute toxicity study to determine LD50 dose of GNP-NN-32, in vivo sub-chronic toxicity for 30 days, haematology, serum biochemical parameters and histopathology study on various mice tissues andin vitro cellular and tissue toxicity studies. Results: The LD50 dose of NN-32 was found to be 2.58 mg/kg (i.p.)in Swiss male albino mice. In vivo sub-chronic toxicity showed significantly reduced toxicity of GNP-NN-32 as compared to NN-32 alone. In vitro cellular toxicity studies on human lymphocyte and mouse peritoneal macrophage showed significant inhibition of cells by NN-32 alone. Conclusion: Conjugated GNP-NN-32 toxin showed less in vivo toxicity as compared to pure NN-32.
Pollution of water bodies by humans, in our day-to-day activities impairs the quality of water, thereby making the water sources unsuitable for aquatic fauna and also for human health. Various sources of pollutants in excess may negatively affect the diversity of living organisms. The evolving growth of nanotechnology has attracted a great deal of attention due to its concern in assessing their environmental and health safety. The present study was conducted to investigate toxicity of copper nanoparticles (CuNP) on the development of fresh water snail Indoplanorbis exustus. Acclimatized snails were exposed to increasing concentration of CuNP for 96 h and acute toxicity experiment was carried out to determine LC50, followed by exposure of snails to sublethal concentrations of CuNP to observe developmental deformities and to estimate percentage hatchability and survivability of young ones. The projected LC50 value for 96h of CuNPs was found to be 5.8mg/L, followed by exposure to sub-lethal concentrations of 1/6th(0.96mg/L), 1/5th(1.16mg/L), 1/4th(1.45mg/L), and 1/3th (1.93mg/L). The highest concentration of (1.93mg/L;1/3thof LC50) retarded hatching and caused morphological deformities in the larvae. However, no significant difference was observed in the weight of embryos in 7 days. These results revealed that CuNP exposure at sub lethal concentrations exerted developmental stress. HIGHLIGHTS Most of the invertebrate models used in aquatic toxicity are from phylum Mollusca, the gastropods are considered as the best model organisms for NPs toxicity because they are adapted to various environmental disturbances due to their dual habitat, easy availability, high fecundity, small size, short generation time and adaptability. Snails, Indoplanorbis exustus were exposed to increasing concentration of copper nanoparticles (CuNPs) for 96 h and acute toxicity experiment was carried out to determine LC50, followed by exposure of snails to sublethal concentrations of CuNPs to observe developmental deformities and to estimate percentage hatchability and survivability of young ones The highest concentration of (1.93 mg/L; 1/3th of LC50) retarded hatching and caused morphological deformities in the larvae. However, no significant difference was observed in the weight of embryos in 7 days. These results revealed that CuNP exposure at sub lethal concentrations exerted developmental stress on snails
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