Repurposing Oxiconazole against Colorectal Cancer via PRDX2-mediated Autophagy Arrest.

Colorectal cancer (CRC) is one of the most common malignancies worldwide, yet successful treatment still remains a challenge. In this study, we found that oxiconazole (OXI), a broad-spectrum antifungal agent, exhibits certain anti-tumor effect against CRC. Autophagy arrest and subsequent apoptosis are characterized as pivotal events involving OXI-induced growth suppression of CRC cells. Mechanistically, OXI downregulates the protein levels of peroxiredoxin-2 (PRDX2), an antioxidant enzyme, for reactive oxygen species (ROS) detoxication, to initiate autophagy by inactivating the Akt/mTOR pathway and inhibiting RAB7A-mediated fusion of autophagosome and lysosome, which lead to extreme accumulation of autophagosomes and subsequent growth suppression of CRC cells. Consistently, interfering with autophagy or overexpressing PRDX2 significantly impedes OXI-induced growth suppression of CRC cells. Moreover, OXI plus oxaliplatin, a mainstay drug for CRC treatment, achieves an improved anti-tumor effect. Taken together, our findings bring novel mechanistic insights into OXI-induced autophagy arrest and the growth inhibitory effect on CRC cells, and suggest a promisingly therapeutic role of OXI for CRC treatment. © The author(s).

Citation

Jinyu Shi, Li Zhou, Hui-Si Huang, Liyuan Peng, Na Xie, Edouard Nice, Li Fu, Cen Jiang, Canhua Huang. Repurposing Oxiconazole against Colorectal Cancer via PRDX2-mediated Autophagy Arrest. International journal of biological sciences. 2022;18(9):3747-3761

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PMID: 35813474

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