Repurposing antitussive benproperine phosphate against pancreatic cancer depends on autophagy arrest

  • Mol Oncol. 2021 Feb;15(2):725-738. doi: 10.1002/1878-0261.12854.
Huanyu Zhang  1  2  3  4 ,  Zhe Zhang  5 ,  Yonghao Huang  1 ,  Siyuan Qin  5 ,  Li Zhou  5 ,  Ningna Weng  5 ,  Jiayang Liu  5 ,  Mei Yang  5 ,  Xiaodian Zhang  1 ,  Yanda Lu  1 ,  Lin Ma  2  4 ,  Shaojiang Zheng  1 ,  Qifu Li  1  2  3  4
Affiliations
  • 1. Key Laboratory of Emergency and Trauma of Ministry of Education & Tumor Institute, the First Affiliated Hospital, Hainan Medical University, Haikou, China.
  • 2. Department of Neurology, the First Affiliated Hospital, Hainan Medical University, Haikou, China.
  • 3. School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, China.
  • 4. Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Haikou, China.
  • 5. State Key Laboratory of Biotherapy and Cancer Center, West China School of Basic Medical Sciences & Forensic Medicine, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
PMID: 33226737 DOI: 10.1002/1878-0261.12854
Abstract

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 a significant Anticancer effect on PC both in vitro and in vivo via the induction of autophagy-mediated cell death. Mechanistic studies revealed that BPP triggered AMPK/mTOR-mediated Autophagy initiation and disturbed Ras-related protein Rab-11A (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. In conclusion, our results identify BPP as a potent antitumor agent for PC via the induction of Autophagy arrest, therefore providing a new potential therapeutic strategy for the treatment of PC.

Keywords
RAB11A; autophagy arrest; benproperine phosphate; drug repurposing; pancreatic cancer.
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