Holo-lactoferrin: the link between ferroptosis and radiotherapy in triple-negative breast cancer

Iron-saturated Lf (Holo-Lactoferrin, Holo-Lf) exhibits a superior anticancer property than low iron-saturated Lf (Apo-Lf). Ferroptosis is an iron-dependent cell death characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). Radiotherapy also exerts i...

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Bibliographic Details
Published in:Theranostics 2021, Vol.11 (7), p.3167-3182
Main Authors: Zhang, Zheng, Lu, Menglan, Chen, Cailong, Tong, Xing, Li, Yunhong, Yang, Kai, Lv, Haitao, Xu, Jiaying, Qin, Liqiang
Format: Article
Language:English
Subjects:
Apoptosis
Biotechnology
Breast cancer
Cancer therapies
Chemotherapy
DNA damage
Ferroptosis
Flow cytometry
Fourier transforms
Free radicals
Hemodialysis
Hypoxia
Lipid peroxidation
Medical prognosis
Microscopy
Nanoparticles
Permeability
Proteins
Quantum dots
Radiation therapy
Reactive oxygen species
Research Paper
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Summary:Iron-saturated Lf (Holo-Lactoferrin, Holo-Lf) exhibits a superior anticancer property than low iron-saturated Lf (Apo-Lf). Ferroptosis is an iron-dependent cell death characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). Radiotherapy also exerts its therapeutic effect through ROS. The effect of different iron-saturated Lf on ferroptosis and radiotherapy were tested on triple-negative breast cancer (TNBC) cell line MDA-MB-231 and non-TNBC cell line MCF-7. Holo-Lf significantly increased the total iron content, promoted ROS generation, increased lipid peroxidation end product, malondialdehyde (MDA), and enhanced ferroptosis of MDA-MB-231 cells. By contrast, Apo-Lf upregulated SLC7a11 expression, increased GSH generation and inhibited ferroptosis of MDA-MB-231 cells. However, non-TNBC MCF-7 cells were resistant to Holo-Lf-induced ferroptosis because MCF-7 cells have a higher redox balance capacity than MDA-MB-231 cells. More importantly, Holo-Lf downregulated HIF-1α expression, ameliorated the hypoxia microenvironment in subcutaneous MDA-MB-231 tumors, and promoted radiation-induced DNA damage to hypoxic MDA-MB-231 cells. Finally, the efficacy of radiotherapy to MDA-MB-231 tumors was enhanced by Holo-Lf. Holo-Lf could induce ferroptosis in MDA-MB-231 cells and sensitize MDA-MB-231 tumors to radiotherapy.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.52028