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Iron Oxide Nanoparticles Induce Ferroptosis Via the Autophagic Pathway by Synergistic Bundling with Paclitaxel

Overview
Journal Mol Med Rep
Specialty Molecular Biology
Date 2023 Sep 8
PMID 37681444
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Abstract

In recent years, inhibiting tumor cell activity by triggering cell ferroptosis has become a research hotspot. The development of generic targeted nanotherapeutics might bring new ideas for non‑invasive applications. Currently, the potential mechanism underlying the universal application of paclitaxel (PTX)‑loaded iron oxide nanoparticles (IONP@PTX) to different types of tumors is unclear. The present study aimed to prepare IONP@PTX for targeted cancer therapy and further explore the potential mechanisms underlying the inhibitory effects of this material on the NCI‑H446 human small cell lung cancer and brain M059K malignant glioblastoma cell lines. First, a CCK‑8 assay was performed to determine cell viability, and then the combination index for evaluating drug combination interaction effect was evaluated. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were monitored using a DCFH‑DA fluorescent probe and a C11‑BODIPY™ fluorescent probe, respectively. Furthermore, western blotting assay was performed to determine the expression of autophagy‑ and iron death‑related proteins. The experimental results showed that, compared with either IONP monotherapy, PTX monotherapy, or IONP + PTX, IONP@PTX exerted a synergistic effect on the viability of both cell types, with significantly increased total iron ion concentration, ROS levels and lipid peroxidation levels. IONP@PTX significantly increased the expression of autophagy‑related proteins Beclin 1 and histone deacetylase 6 (HDAC6) in both cell lines (P<0.05), increased the expression of light chain 3 (LC3)‑II/I in NCI‑H446 cells (P<0.05) and decreased that of sequestosome1 (p62) in M059K cells (P<0.05). Moreover, the addition of rapamycin enhanced the IONP@PTX‑induced the upregulation of Beclin 1, LC3‑II/I and HDAC6 and the downregulation of mTORC1 protein in both cell lines (P<0.05). Moreover, rapamycin enhanced the IONP@PTX‑induced downregulation of p62 protein in NCI‑H446 cells (P<0.05), suggesting that IONP@PTX induces ferroptosis, most likely through autophagy. Collectively, the present findings show that IONP works synergistically with PTX to induce ferroptosis via the autophagic pathway.

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References
1.
Zou Z, Tao T, Li H, Zhu X . mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges. Cell Biosci. 2020; 10:31. PMC: 7063815. DOI: 10.1186/s13578-020-00396-1. View

2.
Li K, Zhan W, Chen Y, Jha R, Chen X . Docetaxel and Doxorubicin Codelivery by Nanocarriers for Synergistic Treatment of Prostate Cancer. Front Pharmacol. 2020; 10:1436. PMC: 6930690. DOI: 10.3389/fphar.2019.01436. View

3.
Sharifi-Rad J, Quispe C, Patra J, Singh Y, Panda M, Das G . Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy. Oxid Med Cell Longev. 2021; 2021:3687700. PMC: 8545549. DOI: 10.1155/2021/3687700. View

4.
Zhu L, Chen L . Progress in research on paclitaxel and tumor immunotherapy. Cell Mol Biol Lett. 2019; 24:40. PMC: 6567594. DOI: 10.1186/s11658-019-0164-y. View

5.
Zhang X, Sui S, Wang L, Li H, Zhang L, Xu S . Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin. J Cell Physiol. 2019; 235(4):3425-3437. DOI: 10.1002/jcp.29232. View