# Targeting iron regulatory protein 2 (IRP2) to disrupt iron metabolism enhances radiosensitivity through mitochondrial dysfunction in breast cancer cells

## TL;DR

Disrupting IRP2 in breast cancer cells can make them more sensitive to radiation therapy by causing mitochondrial dysfunction.

## Contribution

This study proposes IRP2 inhibition as a novel strategy to enhance radiosensitivity in breast cancer.

## Key findings

- Depletion of IRP2 in breast cancer cells increases sensitivity to radiation therapy.
- Inhibiting IRP2 before radiation significantly reduces cell viability in both parental and radioresistant cells.
- IRP2 inhibition induces mitochondrial dysfunction, potentially overcoming resistance to radiation.

## Abstract

Iron regulatory protein (IRP2) plays a key role in regulating iron metabolism and enables cell survival by activating mitochondrial function. Targeting IRP2 to disrupt iron homeostasis is a promising strategy for enhancing the efficacy of cancer treatments. Depletion of IRP2 in breast cancer (BC) cells is associated with sensitivity to radiation therapy (RT), and inhibition of IRP2 prior to RT significantly reduces cell viability compared with radiation treatment alone. This combined therapeutic effects of IRP2 inhibition and radiation treatment were observed in parental and radioresistant cancer cells, significantly enhancing the proportion of cell death. In conclusion, this study proposes that the genetic or pharmacological inhibition of IRP2 in BC cells may serve as a novel therapeutic strategy for increasing radiosensitivity and overcoming resistance by inducing mitochondrial dysfunction.