The Influence of AQP5 on the Response to Hydrogen Peroxide in Breast Cancer Cell Lines

TL;DR

This study explores how AQP5 affects breast cancer cells' response to hydrogen peroxide, revealing cell-type-specific effects on viability and oxidative stress.

Contribution

The study reveals AQP5's cell-type-specific role in modulating oxidative stress responses in breast cancer cells.

Findings

AQP5 overexpression reduced viability in SkBr-3 and MCF7 cells after H2O2 treatment.

ROS levels increased in MCF7-AQP5 but decreased in SUM 159-AQP5 cells.

AQP5 influenced NRF2, FOXO1, and PI3K/AKT signaling pathways differently across cell types.

Abstract

Breast cancer is a heterogeneous disease with varying responses to therapies. While targeted treatments have advanced, conventional therapies inducing oxidative stress remain widely used. H2O2 has emerged as a therapeutic candidate due to its role in signaling and cell-function regulation. Its transport is tightly regulated through peroxiporins such as AQP5, expression of which is linked to poor prognosis and metastatic spread, and its role in therapy resistance remains underexplored. This study examined AQP5’s role in the acute oxidative stress response. We overexpressed AQP5 in breast cancer cell lines with low basal levels—HR+ (MCF7), HER2+ (SkBr-3), and TNBC (SUM 159)—and exposed them to H2O2 for 24 h. We assessed cell viability, intracellular ROS, changes in AQP3 and AQP5, and key antioxidative and cancer-related pathways (NRF2, PI3K/AKT, FOXOs). AQP5 overexpression elicited a cell-type-specific response. H2O2 treatment reduced viability in SkBr-3-AQP5 and MCF7-AQP5 cells, increased ROS levels in MCF7-AQP5, and decreased ROS in SUM 159-AQP5. It also increased AQP3 in MCF7-AQP5 and differentially affected NRF2, FOXOs, and PI3K/AKT signaling, notably activating NRF2/AKR1B10 axis in MCF7-AQP5 and decreasing FOXO1 in SUM 159-AQP5. These findings highlight the need for further research into AQP5’s role in the oxidative stress response in breast cancer cells.

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