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

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

Theranostics (2021-02-05)
Zheng Zhang, Menglan Lu, Cailong Chen, Xing Tong, Yunhong Li, Kai Yang, Haitao Lv, Jiaying Xu, Liqiang Qin
ABSTRACT

Rationale: 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. Methods: 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. Results: 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. Conclusion: Holo-Lf could induce ferroptosis in MDA-MB-231 cells and sensitize MDA-MB-231 tumors to radiotherapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Intracellular Hydrogen Peroxide Assay, sufficient for 200 fluorometric tests (green fluorescence)
Sigma-Aldrich
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder
Sigma-Aldrich
Lactoferrin human, recombinant, expressed in rice, Iron saturated, ≥90% (SDS-PAGE)