Repurposing antitussive benproperine phosphate against pancreatic cancer depends on autophagy arrest.

Pancreatic cancer (PC) is one of the most common human malignancies worldwide and remains a major clinical challenge. Here, we found that Benproperine phosphate (BPP), a cough suppressant, showed significant anti-cancer effect on PC both in vitro and in vivo via induction of autophagy-mediated cell death. Mechanistical studies revealed that BPP triggered AMPK/mTOR-mediated autophagy initiation and disturbed RAB11A-mediated autophagosome-lysosome fusion, resulting in excessive accumulation of autophagosomes. Inhibition of autophagy or overexpression of RAB11A partially reversed BPP-induced growth inhibition in PC cells, suggesting that BPP might induce lethal autophagy arrest in PC cells. Together, our study identifies BPP as a potent anti-tumor agent for PC by inducing autophagy arrest, providing a new potential therapeutic strategy for the treatment of PC.