Fluoxetine induces cytotoxic endoplasmic reticulum stress and autophagy in triple negative breast cancer

Figure 5 Integrated signaling network modulated by fluoxetine in inflammatory triple negative breast cancer line SUM149PT. Proteins with increased and decreased expression levels after FLX treatment were highlighted in red and green, respectively. This proposed that model of FLX-induced cellular stress results in excessive UPR that leads to cell growth inhibition, autophagy, and potentially selective promotion of NFκB-mediated transcription of apoptotic genes, such as Bax. Oligomerization of Bax promotes the release of cytochrome C into cytosol and subsequent activation of caspase-9 and downstream effectors of apoptosis, such as caspase-7[38,40]. Alternatively, Ca²⁺ released during ER stress has been shown to promote cytochrome C release. AMPK: Adenosine monophosphate kinase; UPR: Unfolded protein response; FLX: Fluoxetine; p70 S6K: p70 S6 Kinase; ER: Endoplasmic reticulum.