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

Chong Zhao | ShaoZhuang Qiu | Jie He | Yao Peng | Haoming Xu | Zhiqiang Feng | Hongli Huang | Yanlei Du | Yongjian Zhou | Yuqiang Nie
Cancer letters | 2020

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.

Pubmed ID: 32184145

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