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


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.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC7858282 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Zhang Huanyu H   Zhang Zhe Z   Huang Yonghao Y   Qin Siyuan S   Zhou Li L   Weng Ningna N   Liu Jiayang J   Yang Mei M   Zhang Xiaodian X   Lu Yanda Y   Ma Lin L   Zheng Shaojiang S   Li Qifu Q  

Molecular oncology 20201212 2


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  ...[more]

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