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Superparamagnetic Iron Oxide Nanoparticles Induce Apoptosis in HT-29 Cells by Stimulating Oxidative Stress and Damaging DNA

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Abstract

Nanoparticles have garnered considerable scientific attention in recent years due to their diagnostic and therapeutic applications in cancer. The purpose of this study was to determine the effect of superparamagnetic iron oxide nanoparticles (Fe3O4 MNPs) on the induction of apoptosis in human colorectal adenocarcinoma cell line (HT-29) cells. The purpose of this study was to elucidate the mechanisms of apoptosis induced by Fe3O4 MNPs following MTT assay and to determine the optimal dose of 2.5 g/mL for inducing apoptosis in HT-29 cells. In HT-29 cells, Fe3O4 MNPs increased reactive oxygen species (ROS), calcium ion (Ca2+), and DNA damage. Additionally, the Fe3O4 MNPs significantly increased caspase 3 and 9 expression and decreased Bcl-2 expression at the protein and mRNA levels when compared to the control group (P = 0.0001). Fe3O4 MNPs also induced apoptosis in cancer cells by increasing the level of (ROS) and intracellular Ca2+, followed by an increase in caspase 3 and 9 expression and a decrease in Bcl-2 expression and direct DNA damage. Fe3O4 MNPs are an appropriate choice for colon cancer treatment based on their cell toxicity and induction of apoptosis in HT29 cells.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Fe3O4 MNPs:

Superparamagnetic iron oxide nanoparticles

HT-29:

Human colorectal adenocarcinoma cell line (ATCC HTB-38)

ROS:

Reactive oxygen species

Bcl-2:

B cell lymphoma 2

Bax:

BCL2-associated X

PI:

Propidium iodide

DAPI:

4′,6-Diamidino-2-phenylindole

BrdU:

Bromodeoxyuridine/5-bromo-2′-deoxyuridine

NP:

Nanoparticle

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgements

The authors thank Dr. Reza Rastegar University of Tehran Laboratory and Ferdowsi University of Mashhad Central Laboratory for their cooperation.

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Mohammadreza Azimi, Jalil Mehrzad, Golnaz Karbalaei Saleh and Ali Ghorbani Ranjbary performed the experiments, conceived and designed the study, and wrote, analyzed, funded, and critically revised the manuscript. Fatemeh karimian and Javad zohdi also actively helped in the experiments and participated in study design, study implementation, and manuscript revision.

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Correspondence to Ali Ghorbani Ranjbary.

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Ranjbary, A.G., Saleh, G.K., Azimi, M. et al. Superparamagnetic Iron Oxide Nanoparticles Induce Apoptosis in HT-29 Cells by Stimulating Oxidative Stress and Damaging DNA. Biol Trace Elem Res 201, 1163–1173 (2023). https://doi.org/10.1007/s12011-022-03229-z

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