Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage

Background: The most prevalent pediatric cancer is acute lymphoblastic leukemia (ALL). It is exceedingly challenging to treat recurrent diseases, and there aren’t many new medications available for children with disease resistance. The size-dependent anticancer effect of zinc oxide nanoparticles (Zn...

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Main Authors: Venugopal Sujatha, Alagesan Venkatesan, Acharya Sancharan, Chinnasamy Thirunavukkarasu
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2024-04-01
Series:Pharmaceutical Sciences
Subjects:
Online Access:https://ps.tbzmed.ac.ir/PDF/ps-30-262.pdf
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author Venugopal Sujatha
Alagesan Venkatesan
Acharya Sancharan
Chinnasamy Thirunavukkarasu
author_facet Venugopal Sujatha
Alagesan Venkatesan
Acharya Sancharan
Chinnasamy Thirunavukkarasu
author_sort Venugopal Sujatha
collection DOAJ
description Background: The most prevalent pediatric cancer is acute lymphoblastic leukemia (ALL). It is exceedingly challenging to treat recurrent diseases, and there aren’t many new medications available for children with disease resistance. The size-dependent anticancer effect of zinc oxide nanoparticles (ZnONPs) on T-cell acute lymphoblastic leukemia (T-ALL) cell line MOLT 3 is the central theme of this study. Methods: The leaf and bark extracts of Diospyros montana were subjected to nanoparticle (NPs) synthesis and characterized analytically to acquire ZnONPs. The ZnONPs were characterized using UV-Vis spectra, DLS, XRD, EDX, SEM, and TEM analysis. Then the ZnONPs were separated into two groups having <50 nm and 50-100 nm NPs sizes. In addition, MTT assay, dual staining, autophagy, DNA damage, and oxidative damage measurement were done to find out the anti-cancer effect of the ZnONPs on MOLT 3 cells. Results: The ZnONPs exhibited a size-dependent anticancer effect against MOLT 3 cells. The IC50 of ZnONPs of < 50 nm was found to be ~75 µg/mL while the IC50 of ZnONPs of 50-100 nm size was found to be ~102 µg/mL. Treatment with ZnONPs of <50 nm size decreased mitochondrial membrane potential, more than that with 50-100 nm ZnONPs. On the other hand, autophagy was found to be more prevalent in 50-100 nm treated ZnONPs when compared with < 50 nm size. However, treatment with both sizes of ZnONPs reduced cell proliferation markers such as ki67 positive cells while increasing 8-OHG and HDCF-DA positive cells. Conclusion: The obtained results portrayed that different-sized ZnONPs induce different modes of T-ALL cell death. Small-sized ZnONPs revealed higher efficacy, highlighting the size-dependent property. Further, this finding denotes that ZnONPs could be an effective anticancer agent against dreadful diseases like T-ALL, warranting further investigation.
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spelling doaj.art-3a969ba47c4d4c7e8c955bfbbe31e3e02024-04-13T10:40:54ZengTabriz University of Medical SciencesPharmaceutical Sciences2383-28862024-04-0130226227310.34172/PS.2024.4ps-40044Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA DamageVenugopal Sujatha0Alagesan Venkatesan1Acharya Sancharan2Chinnasamy Thirunavukkarasu3Department of Chemistry, Pondicherry University, Puducherry-605014, IndiaDepartment of Chemistry, Pondicherry University, Puducherry-605014, IndiaDepartment of Biochemistry and Molecular Biology, Pondicherry University, Puducherry-605014, IndiaDepartment of Biochemistry and Molecular Biology, Pondicherry University, Puducherry-605014, IndiaBackground: The most prevalent pediatric cancer is acute lymphoblastic leukemia (ALL). It is exceedingly challenging to treat recurrent diseases, and there aren’t many new medications available for children with disease resistance. The size-dependent anticancer effect of zinc oxide nanoparticles (ZnONPs) on T-cell acute lymphoblastic leukemia (T-ALL) cell line MOLT 3 is the central theme of this study. Methods: The leaf and bark extracts of Diospyros montana were subjected to nanoparticle (NPs) synthesis and characterized analytically to acquire ZnONPs. The ZnONPs were characterized using UV-Vis spectra, DLS, XRD, EDX, SEM, and TEM analysis. Then the ZnONPs were separated into two groups having <50 nm and 50-100 nm NPs sizes. In addition, MTT assay, dual staining, autophagy, DNA damage, and oxidative damage measurement were done to find out the anti-cancer effect of the ZnONPs on MOLT 3 cells. Results: The ZnONPs exhibited a size-dependent anticancer effect against MOLT 3 cells. The IC50 of ZnONPs of < 50 nm was found to be ~75 µg/mL while the IC50 of ZnONPs of 50-100 nm size was found to be ~102 µg/mL. Treatment with ZnONPs of <50 nm size decreased mitochondrial membrane potential, more than that with 50-100 nm ZnONPs. On the other hand, autophagy was found to be more prevalent in 50-100 nm treated ZnONPs when compared with < 50 nm size. However, treatment with both sizes of ZnONPs reduced cell proliferation markers such as ki67 positive cells while increasing 8-OHG and HDCF-DA positive cells. Conclusion: The obtained results portrayed that different-sized ZnONPs induce different modes of T-ALL cell death. Small-sized ZnONPs revealed higher efficacy, highlighting the size-dependent property. Further, this finding denotes that ZnONPs could be an effective anticancer agent against dreadful diseases like T-ALL, warranting further investigation.https://ps.tbzmed.ac.ir/PDF/ps-30-262.pdfacute lymphoblastic leukemiadna damagediospyros montanamolt3oxidative stresszinc oxide nanoparticles
spellingShingle Venugopal Sujatha
Alagesan Venkatesan
Acharya Sancharan
Chinnasamy Thirunavukkarasu
Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage
Pharmaceutical Sciences
acute lymphoblastic leukemia
dna damage
diospyros montana
molt3
oxidative stress
zinc oxide nanoparticles
title Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage
title_full Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage
title_fullStr Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage
title_full_unstemmed Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage
title_short Biogenic Zinc Oxide Nanoparticles Attenuate Acute Lymphoblastic Leukemia Cell Proliferation through Oxidative Stress and DNA Damage
title_sort biogenic zinc oxide nanoparticles attenuate acute lymphoblastic leukemia cell proliferation through oxidative stress and dna damage
topic acute lymphoblastic leukemia
dna damage
diospyros montana
molt3
oxidative stress
zinc oxide nanoparticles
url https://ps.tbzmed.ac.ir/PDF/ps-30-262.pdf
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