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Gossypol Inhibits Metastasis of Lung Cell Carcinoma by Reversing Epithelial to Mesenchymal Transition and Suppressing
Yih-Shou Hsieh1, Ching-Han Yu2, Shu-Chen Chu3
1Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Abstract:
Gossypol, a natural polyphenolic compound, possesses antivirus activity and induces cell death of different types of tumors. However, the efficacy of gossypol on lung carcinoma metastases and epithelial to mesenchymal transition remains unknown. The aim of the present work was to determine the cellular and molecular mechanism of the anti-cancer and anti-metastatic efficacies of gossypol on human lung carcinoma cells. Gossypol showed a marked suppression of the viability, motility, and invasion in H1299 and A549 cells. Zymography assay showed that gossypol was sufficient to suppress the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2. Gossypol reversed TGF-β-induced epithelial to mesenchymal transition. Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice.
Insights
Gossypol effectively inhibits lung carcinoma cell viability, motility, and invasion. This natural compound also reverses epithelial to mesenchymal transition, offering potential as an anti-cancer and anti-metastatic agent.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Gossypol, a natural polyphenolic compound, exhibits known antiviral and anti-tumor properties.
- The anti-metastatic and anti-epithelial-to-mesenchymal transition (EMT) effects of gossypol on lung carcinoma are not well understood.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying the anti-cancer and anti-metastatic effects of gossypol on human lung carcinoma cells.
- To evaluate gossypol's impact on cell viability, motility, invasion, and EMT.
Main Methods:
- Cell viability, motility, and invasion assays were performed on H1299 and A549 lung carcinoma cell lines.
- Zymography was used to assess urokinase-type plasminogen activator and matrix metalloproteinase-2 activity.
- Western blotting was employed to analyze protein expression changes, including vimentin, p-FAK, p-Src, and p-paxillin.
- In vivo studies involved subcutaneous inoculation and tail vein injection of A549 cells in immunodeficient mice.
Main Results:
- Gossypol significantly suppressed the viability, motility, and invasion of H1299 and A549 lung carcinoma cells.
- Gossypol inhibited the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2.
- Gossypol effectively reversed transforming growth factor-beta (TGF-β)-induced epithelial to mesenchymal transition (EMT).
- Gossypol treatment led to reduced levels of vimentin, p-FAK, p-Src, and p-paxillin, key markers of EMT and cell signaling.
Conclusions:
- Gossypol demonstrates significant anti-cancer and anti-metastatic potential against human lung carcinoma.
- Gossypol exerts its effects by suppressing cell viability, motility, invasion, and reversing EMT.
- The findings suggest gossypol as a promising therapeutic candidate for lung cancer treatment.
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