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

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.