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      Anticancer potential of nanogold conjugated toxin GNP-NN-32 from Naja naja venom

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          Abstract

          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.

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          Most cited references42

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          Cancer and Radiation Therapy: Current Advances and Future Directions

          In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.
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            Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis.

            Mitochondria are functionally and physically associated with heterotypic membranes, yet little is known about how these interactions impact mitochondrial outer-membrane permeabilization (MOMP) and apoptosis. We observed that dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX-dependent cytochrome c (cyto c) release. Biochemical purification of neutral sphingomyelinases that correlated with MOMP sensitization suggested that sphingolipid metabolism coordinates BAK/BAX activation. Using purified lipids and enzymes, sensitivity to MOMP was achieved by in vitro reconstitution of the sphingolipid metabolic pathway. Sphingolipid metabolism inhibitors blocked MOMP from heavy membrane preparations but failed to influence MOMP in the presence of sphingolipid-reconstituted, purified mitochondria. Furthermore, the sphingolipid products, sphingosine-1-PO(4) and hexadecenal, cooperated specifically with BAK and BAX, respectively. Sphingolipid metabolism was also required for cellular responses to apoptosis. Our studies suggest that BAK/BAX activation and apoptosis are coordinated through BH3-only proteins and a specific lipid milieu that is maintained by heterotypic membrane-mitochondrial interactions. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Anticancer drug targets: cell cycle and checkpoint control.

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                Author and article information

                Journal
                J Venom Anim Toxins Incl Trop Dis
                J Venom Anim Toxins Incl Trop Dis
                jvatitd
                The Journal of Venomous Animals and Toxins Including Tropical Diseases
                Centro de Estudos de Venenos e Animais Peçonhentos
                1678-9199
                02 March 2020
                2020
                : 26
                : e20190047
                Affiliations
                [1 ]Evolutionary Venomics Laboratory, Centre for Ecological Sciences, Indian Institute of Science, Bangalore, Karnataka, India.
                [2 ]Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India.
                Author notes

                Competing interests: The authors declare that they have no competing interests.

                Authors’ contributions: SA performed all the experiments. SA and SP designed the experiments. All authors read and approved the final manuscript.

                Author information
                http://orcid.org/0000-0003-2632-6837
                http://orcid.org/0000-0003-3370-9852
                Article
                00304
                10.1590/1678-9199-JVATITD-2019-0047
                7059613
                32180805
                7089ca84-97be-4661-a94c-fb25ca735148

                © The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 02 August 2019
                : 27 November 2019
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 46
                Categories
                Research

                gnp-nn-32,anticancer,toxin,naja naja,venom,breast cancer,mcf-7,mda-mb-231

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