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Chitosan-encapsulated naringenin promotes ROS mediated through the activation of executioner caspase-3

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Abstract

We previously reported that chitosan nanoparticle-encapsulated Naringenin (CS-NPs/NAR) could scavenge free radicals at lower doses and be cytotoxic to cancer cells. The current study continues to focus on the mechanism behind CS-NPs/NAR-induced breast cancer cell (MDA-MB-231) death. MDA-MB-231 cells were treated with higher concentrations (100, 200, and 200 µg) of Chitosan nanoparticles (CS-NPs), naringenin (NAR), and chitosan-encapsulated naringenin (CS-NPs/NAR). The cell viability, proliferation, and oxidative stress parameters, such as nitric oxide [NO], xanthine oxidase (XOD), and xanthine dehydrogenase (XDH) levels, were analyzed. ROS levels were determined through DCFDA analysis. MTT-based cell cytotoxicity and BrdU cell proliferation analysis depicted the cytotoxicity effects (37% and 29% for 24 and 48 h) and exhibited a reduction in the proliferation of MDA-MB-231 by CS-NPs/NAR. A significant increase in NO content, XOD, a decrease in XDH, and an increase in ROS levels were observed upon treatment with CS-NPs/NAR. Fluorescent images suggested the increase in the ROS level upon treatment with CS-NPs/NAR in cancer cells, and the results suggested that it could induce apoptosis. Further, to confirm this, the activity of caspase-3 was analyzed through western blotting, and the result suggested that the higher concentration of CS-NPs/NAR has increased the activation of procaspase3 when compared to free NAR. Hence, the current investigation concludes that high doses of CS-NPs/NAR induce and increase oxidative stress and so increased activation of procaspase3 may lead to cancer cell apoptosis and reduction in cell proliferation.

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This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. K. T. Ramya Devi and M. K. Jaganathan have contributed equally to this work.

Authors and Affiliations

  1. Faculty of Engineering and Technology, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India

    K. T. Ramya Devi, M. K. Jaganathan & Karthick Dharshene

  2. Department of Chemistry, College of Enginering and Technology, SRM institute of Science and Technology, Interdisciplinary Institute of Indian System of Medicine, Kattankulathur, Chennai, Tamil Nadu, 603203, India

    M. R. Ganesh

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Contributions

KTR and MKJ: designed this work. MRG has done the work based on FACS and confocal images, and the technical help had been taken from KD for fluorescent imaging. The manuscript was written by KTR and reviewed by KTR and MKJ.

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Correspondence to K. T. Ramya Devi.

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Ramya Devi, K.T., Jaganathan, M.K., Ganesh, M.R. et al. Chitosan-encapsulated naringenin promotes ROS mediated through the activation of executioner caspase-3. Med Oncol 41, 3 (2024). https://doi.org/10.1007/s12032-023-02227-y

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