Zinc Oxide Nanoparticles Synthesized by Bacillus cereus PMSS-1 Induces Oxidative Stress-Mediated Apoptosis via Modulatin

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Zinc Oxide Nanoparticles Synthesized by Bacillus cereus PMSS-1 Induces Oxidative Stress-Mediated Apoptosis via Modulating Apoptotic Proteins in Human Melanoma A375 Cells Ramya Parthasarathy1 • Rajalakshmi Ramachandran1 • Yoganathan Kamaraj1 • Sangeetha Dhayalan1 Received: 1 May 2020 / Accepted: 5 November 2020  Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract The microbial mediated synthesis of nanoparticles will be more effective for chemotherapeutic applications because microbes are well known attractive sources for the various biologically active biomolecules. The present study was designed to investigate the anticancer effect of zinc oxide nanoparticles (ZnO NPs) synthesized by Bacillus cereus PMSS-1 strain on human melanoma A375 cells. The synthesized ZnO NPs was characterized by UV-spectroscopy, X-ray diffraction (XRD) investigation, transmission electron microscope (TEM), energy dispersive X-ray (EDX), and Fourier transform infrared (FTIR) examination. The results show that the ZnO NPs exhibited concentration-dependent cytotoxicity on A375 cells, and induced the apoptosis as evidenced by the increased lipid peroxidation (LPO), diminished activities of an antioxidant such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Moreover, the administration of synthesized ZnO NPs increased reactive oxygen species (ROS) production and reduced mitochondrial membrane potential (MMP) in A375 cells. The western blot analyses explored that the anti-apoptotic protein Bcl-2 expression was significantly downregulated, whereas, the expression of pro-apoptotic proteins such as p53, Bax, Caspase-3 and Caspase-9 were significantly upregulated in ZnO NPs treated A375 cells. Therefore, the B. cereus synthesized ZnO NPs could be used for human malignant melanoma after proper in vivo studies. Keywords Melanoma  Bacillus cereus  ZnO NPs  p53  Bcl-2

Introduction Melanoma is a malignant transformation of pigmented cells of skin called melanocytes located in the epidermis [1–3]. The early stage of melanoma was curable with appropriate treatments; however, the metastasis melanoma has an unfavorable for prognosis and difficult to cure. On account of this, the metastatic melanoma patient’s life span has greatly reduced, which is ranges from 4.7 to 11 months [4]. Due to the drug resistance of malignant melanoma cells, it becomes difficult to cure with the currently available chemotherapeutic drug, which contributes to minimize

& Sangeetha Dhayalan [email protected] 1

Department of Microbiology, Faculty of Science, Annamalai University, Annamalai Nagar, Chidambaram 608002, Tamilnadu, India

the survival of the melanoma patients. Moreover, the available chemotherapeutic drug exerts some side effects. On account of this, it is important to find the new chemotherapeutic agent which able to selectively destroy the malignant melanoma cells by overcoming the drug resistance. Nanomedicine is a field of nanotechnology possibly applicab