2. Academic Validation
  3. Prodigiosin impairs autophagosome-lysosome fusion that sensitizes colorectal cancer cells to 5-fluorouracil-induced cell death

Prodigiosin impairs autophagosome-lysosome fusion that sensitizes colorectal cancer cells to 5-fluorouracil-induced cell death

  • Cancer Lett. 2020 Jul 1;481:15-23. doi: 10.1016/j.canlet.2020.03.010.
Chong Zhao 1,  ShaoZhuang Qiu 1,  Jie He 1,  Yao Peng 1,  Haoming Xu 1,  Zhiqiang Feng 1,  Hongli Huang 1,  Yanlei Du 1,  Yongjian Zhou 1,  Yuqiang Nie 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China; Department of Gastroenterology, Guangzhou First People's Hospital, School of Medical, South China University of Technology, Guangzhou, 510180, China.
  • 2 Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China; Department of Gastroenterology, Guangzhou First People's Hospital, School of Medical, South China University of Technology, Guangzhou, 510180, China. Electronic address: eynieyuqiang@scut.edu.cn.
PMID: 32184145 DOI: 10.1016/j.canlet.2020.03.010
Abstract

Chemotherapy failure is a major cause of recurrence and poor prognosis in colorectal Cancer (CRC) patients. Inhibition of Autophagy is a promising strategy to augment the cytotoxicity of chemotherapeutic agents. We identified prodigiosin, a secondary metabolite produced by various bacteria, as a novel Autophagy Inhibitor that interfered with the autophagic flux in CRC cells by blocking autophagosome-lysosome fusion and lysosomal Cathepsin maturation, resulting in the accumulation of LC3B-II and SQSTM. Suppression of Autophagy by prodigiosin sensitized the CRC cells to 5-fluorouracil (5-Fu) in vitro, and the combination treatment markedly reduced Cancer cell viability partly via caspase-dependent Apoptosis. Furthermore, prodigiosin and 5-Fu synergistically inhibited CRC xenograft growth in vivo without any adverse effects. In conclusion, prodigiosin inhibits late stage Autophagy and sensitizes tumor cells to 5-Fu, indicating its therapeutic potential in CRC.

Keywords

Apoptosis; Autophagy flux; Chemotherapy; Colorectal cancer; Prodigiosin.

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