2. Academic Validation
  3. Corynoxine suppresses pancreatic cancer growth primarily via ROS-p38 mediated cytostatic effects

Corynoxine suppresses pancreatic cancer growth primarily via ROS-p38 mediated cytostatic effects

  • Br J Cancer. 2022 Oct 13. doi: 10.1038/s41416-022-02002-2.
Chunmei Wen # 1,  Qingqing Ruan # 1,  Zhaofeng Li 2,  Xiang Zhou 3,  Xuezhi Yang 4,  Pingwei Xu 5,  Percy David Papa Akuetteh 6,  Zheng Xu 7,  Jie Deng 8
Affiliations

Affiliations

  • 1 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China.
  • 2 Department of Preventive Medicine, Institute of Nutrition and Diseases, Wenzhou Medical University, 325035, Wenzhou, China.
  • 3 Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China.
  • 4 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China.
  • 5 Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China.
  • 6 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China.
  • 7 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China. [email protected].
  • 8 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China. [email protected].
  • # Contributed equally.
PMID: 36229578 DOI: 10.1038/s41416-022-02002-2
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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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