# Targeting Autophagy and the Anticipatory Unfolded Protein Response Leads to Increased Breast Cancer Cell Death

## TL;DR

A compound called BHPI triggers cell death in breast cancer cells by targeting two cellular processes, and combining it with autophagy inhibition could improve cancer treatment.

## Contribution

The study shows that combining BHPI treatment with autophagy inhibition significantly increases breast cancer cell death.

## Key findings

- BHPI induces necrotic cell death in ERα-positive breast cancer cells.
- BHPI depletes cellular ATP, and autophagy inhibition enhances its effect.
- Combining aUPR targeting with autophagy inhibition increases cell death in T47D and TYS cells.

## Abstract

Activation of the anticipatory unfolded protein response (aUPR) by the small molecule 3,3-bis(4-hydroxyphenyl)-7-methyl-1,3,dihydro-2H-indol-2-one (BHPI) leads to necrotic cell death in a variety of cancer cells containing Estrogen Receptor alpha (ERα). A key feature of BHPI’s mechanism of action is depletion of cellular ATP. Other pathways such as autophagy can regulate cellular energy levels and ATP production. We present data that suggests targeting both the aUPR and autophagy leads to a significant increase in cell death in T47D and TYS breast cancer cells treated with BHPI. This combination presents itself as a possible therapeutic strategy against breast cancer.