2. Academic Validation
  3. Repurposing antitussive benproperine phosphate against pancreatic cancer depends on autophagy arrest

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

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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