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Published on: March 18, 2015
Corynoxine suppresses pancreatic cancer growth primarily via ROS-p38 mediated cytostatic effects
Chunmei Wen1, Qingqing Ruan1, Zhaofeng Li2
1Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China.
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.
Insights
Corynoxine (Cory) demonstrates anti-tumour effects against pancreatic cancer by inhibiting cell proliferation and inducing apoptosis. This compound shows promise as a potential therapeutic agent for pancreatic cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Pancreatic cancer is a leading cause of cancer mortality with limited effective treatments.
- Corynoxine (Cory), known to induce autophagy in neuronal cells, has not been investigated for its anti-cancer potential in pancreatic cancer.
Purpose of the Study:
- To investigate the anti-tumour activities of Corynoxine (Cory) against pancreatic cancer cell lines.
- To elucidate the underlying mechanisms of Cory's anti-cancer effects.
Main Methods:
- Utilized human pancreatic cancer cell lines (Patu-8988, Panc-1) for in vitro studies.
- Assessed cell viability, proliferation, apoptosis, and colony formation.
- Analyzed mRNA and protein expression via qPCR and Western blot.
- Evaluated in vivo anti-tumour efficacy using a xenograft mouse model.
Main Results:
- Cory treatment significantly inhibited pancreatic cancer cell proliferation and induced apoptosis.
- Cory induced endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production.
- Inhibition of ER stress partially rescued Cory-induced apoptosis, while ROS scavenging and p38 pathway inhibition reduced Cory's anti-proliferative effects.
- Cory demonstrated significant tumour growth inhibition in vivo.
Conclusions:
- Corynoxine exhibits anti-tumour effects in pancreatic cancer, primarily through ROS-p38 mediated cytostatic mechanisms.
- Cory may represent a promising therapeutic candidate for pancreatic cancer.
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