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Cellular and Molecular Biology

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

British Journal of Cancer volume 127, pages 2108–2117 (2022)Cite this article

Subjects

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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Fig. 1: The anti-proliferative effects of Cory on PDAC cells.
Fig. 2: Cory promotes apoptosis in PDAC cells.
Fig. 3: Cory promotes ER stress- and CHOP-dependent apoptosis in PDAC cells.
Fig. 4: Cory induces apoptosis via ROS-dependent ER stress in PDAC cells.
Fig. 5: Cory induces ROS-dependent apoptosis through p38 activation in PDAC cells.
Fig. 6: Cory inhibits tumour growth in a xenograft model of PDAC.

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Data availability

The data of this study are available within the article and in Supplementary Materials.

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Funding

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).

Author information

Author notes

  1. These authors contributed equally: Chunmei Wen, Qingqing Ruan.

Authors and 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

    Chunmei Wen, Qingqing Ruan, Zheng Xu & Jie Deng

  2. Department of Preventive Medicine, Institute of Nutrition and Diseases, Wenzhou Medical University, 325035, Wenzhou, China

    Zhaofeng Li

  3. Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China

    Xiang Zhou

  4. Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China

    Xuezhi Yang

  5. Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China

    Pingwei Xu

  6. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China

    Percy David Papa Akuetteh

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Contributions

JD, ZX, and XY designed the project; CW, QR, and XY performed the molecular biology and cell biology experiments and analysed data. ZL and XZ performed in vivo experiments. JD, ZX, and CW wrote the manuscript. PDPA contributed to the manuscript editing. All authors contributed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Zheng Xu or Jie Deng.

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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

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