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Corynoxine triggers cell death via activating PP2A and regulating AKT-mTOR/GSK3β axes in NSCLC
Guoqing Hou1, Weihua Hu2, Yazhou Sang3
1School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; School of Medicine, Taizhou University, Taizhou 318000, Zhejiang, China.
Abstract:
This study investigates the anticancer activity and pharmacological mechanisms of Corynoxine (Cory) in non-small cell lung cancer (NSCLC). Cory, a natural product derived from the Chinese herbal medicine Uncaria rhynchophylla, demonstrates promising pharmacological activity. Cell proliferation and viability were evaluated via MTT and colony formation assays. Flow cytometry was employed to analyze cell apoptosis, cycle distribution, and mitochondrial membrane potential. Autophagy was detected using fluorescence microscopy and electron microscopy. Western blotting, protein overexpression, gene knockdown, co-immunoprecipitation, and bioinformatics characterized Cory's impact on signaling pathways. The research indicates that Cory inhibits the proliferation of NSCLC cells in vivo and in vitro. Cory enhances PP2A activity, inhibits the AKT/mTOR signaling pathway triggering autophagy, while suppressing the AKT/GSK3β signaling pathway to induce cellular apoptosis in NSCLC. Notably, the activation of PP2A plays a crucial role in Cory's antitumor effects by inhibiting AKT. In vivo experiments validated Cory's efficacy in NSCLC treatment. These findings highlight the promising role of Cory as a lead compound for drug development in NSCLC therapy, providing a viable option for addressing this challenging disease.
Insights
Corynoxine (Cory), a natural compound, effectively inhibits non-small cell lung cancer (NSCLC) growth. It triggers apoptosis and autophagy by modulating key signaling pathways, offering a promising new therapeutic avenue for NSCLC treatment.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
- There is a continuous need for novel therapeutic agents with improved efficacy and reduced toxicity.
- Natural products, such as Corynoxine (Cory) from Uncaria rhynchophylla, represent a potential source for anticancer drug discovery.
Purpose of the Study:
- To investigate the anticancer activity of Corynoxine (Cory) in non-small cell lung cancer (NSCLC).
- To elucidate the pharmacological mechanisms underlying Cory's effects on NSCLC cells.
- To evaluate Cory's potential as a lead compound for NSCLC drug development.
Main Methods:
- Cell proliferation and viability assays (MTT, colony formation).
- Flow cytometry for apoptosis, cell cycle, and mitochondrial membrane potential analysis.
- Microscopy (fluorescence, electron) for autophagy detection.
- Western blotting, gene manipulation, co-immunoprecipitation, and bioinformatics for pathway analysis.
Main Results:
- Cory inhibits NSCLC cell proliferation both in vitro and in vivo.
- Cory enhances protein phosphatase 2A (PP2A) activity, leading to AKT inhibition.
- Cory triggers autophagy via the AKT/mTOR pathway and induces apoptosis via the AKT/GSK3β pathway.
- In vivo studies confirm Cory's therapeutic efficacy in NSCLC models.
Conclusions:
- Corynoxine exhibits significant anticancer activity against NSCLC.
- Cory's mechanism involves PP2A activation, modulating AKT signaling to induce apoptosis and autophagy.
- Cory holds promise as a potential lead compound for developing novel NSCLC therapies.
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