Pancreatic cancer is among the most common malignant tumours, and effective therapeutic strategies are still lacking. While Corynoxine (Cory) can induce autophagy in neuronal cells, it remains unclear whether Cory has anti-tumour activities against pancreatic cancer.
Two pancreatic cancer cell lines, Patu-8988 and Panc-1, were used. Effects of Cory were evaluated by cell viability analysis, EdU staining, TUNEL assay, colony formation assay, and flow cytometry. Quantitative PCR and Western blot were performed to analyse mRNA and protein levels, respectively. In vivo anti-tumour efficacy of Cory was determined by a xenograft model.
Cory treatment inhibited cell proliferation, induced endoplasmic reticulum (ER) stress, and triggered apoptosis in the pancreatic cancer cell lines. CHOP knockdown-mediated inhibition of ER stress alleviated the Cory-induced apoptosis but showed a limited effect on cell viability. Cory induced cell death partially via promoting reactive oxygen species (ROS) production and activating p38 signalling. Pretreatment with ROS scavenger N-acetylcysteine and p38 inhibitor SB203580 relieved the Cory-induced inhibition on cell growth. Cory remarkably blocked pancreatic tumour growth in vivo.
Cory exerts an anti-tumour effect on pancreatic cancer primarily via ROS-p38-mediated cytostatic effects. Cory may serve as a promising therapeutic agent for pancreatic cancer.
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This work was supported by the National Natural Science Foundation of China (grant number 82102983), Wenzhou Municipal Science and Technology Bureau (grant number Y20210234), and the Fundamental Research Funds for Wenzhou Medical University (grant number KYYW202019).
The authors declare no competing interests.
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All animal procedures were performed according to the Institutional laboratory animal research guidelines and were approved by Wenzhou Medical University Animal Policy and Welfare Committee. This study conformed to the principles outlined in the Declaration of Helsinki.
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Wen, C., Ruan, Q., Li, Z. et al. Corynoxine suppresses pancreatic cancer growth primarily via ROS-p38 mediated cytostatic effects. Br J Cancer 127, 2108–2117 (2022). https://doi.org/10.1038/s41416-022-02002-2