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Veratramine Inhibits Human Non-Small Cell Lung Cancer Cell Growth by Inhibiting the Hedgehog Signaling Pathway
Seoung-Woo Lee1,2, Hee-Yeon Kim1,3, Wansoo Kim4
1Core Protein Resources Center, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
Objectives:
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in both males and females. Considering the growing impact of NSCLC on public health, there is an urgent need for additional treatment strategies. Veratramine, a natural steroidal alkaloid extracted from the roots of plants in the lily family, has recently garnered attention regarding its potential anti-cancer effects. However, to the best of our knowledge, the role of veratramine in the progression of lung cancer is unclear.
Methods:
The various concentration of veratramine were applied to the NSCLC cell lines (A549, NCI-H358 and NCI-H1299). The cell viability, apoptosis, and the cell cycle were evaluated using CCK-8 and flow cytometry assays. Phenotype of NSCLC cells were examined using an optical microscope and ImageJ software. Protein expression in veratramine-treated NSCLC cells was measured using immunoblotting.
Results:
Veratramine-treated NSCLC cells exhibited significantly reduced cell viability and migration ability. Flow cytometry (i.e., fluorescence-activated cell sorting) revealed that treatment with veratramine increased apoptosis and cell cycle delay. Immunoblotting indicated that the Hedgehog (Hh) signaling pathway was significantly downregulated via inhibiting gli1 expression. Cell cycle-related proteins in NSCLC cells were decreased by veratramine treatment.
Conclusion:
Veratramine suppresses lung cancer cell growth by inhibiting the Hh signaling pathway, suggesting its potential applicability in the treatment of NSCLC.
Insights
Veratramine, a natural compound, was found to inhibit non-small cell lung cancer (NSCLC) cell growth and migration. This natural steroidal alkaloid also promotes apoptosis and delays the cell cycle by downregulating the Hedgehog signaling pathway.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
- There is a critical need for novel therapeutic strategies to combat NSCLC.
- Veratramine, a steroidal alkaloid from lily plants, shows potential anti-cancer properties, but its role in NSCLC is not well-defined.
Purpose of the Study:
- To investigate the effects of veratramine on NSCLC cell lines.
- To elucidate the underlying molecular mechanisms of veratramine's action in NSCLC.
Main Methods:
- NSCLC cell lines (A549, NCI-H358, NCI-H1299) were treated with varying concentrations of veratramine.
- Cell viability, apoptosis, and cell cycle progression were assessed using CCK-8 and flow cytometry.
- Protein expression, including components of the Hedgehog signaling pathway, was analyzed via immunoblotting.
Main Results:
- Veratramine significantly reduced NSCLC cell viability and migration.
- Treatment with veratramine induced apoptosis and caused cell cycle arrest.
- The Hedgehog (Hh) signaling pathway was downregulated, evidenced by decreased gli1 expression and reduced cell cycle-related proteins.
Conclusions:
- Veratramine exhibits anti-cancer effects against NSCLC by suppressing cell growth and migration.
- Inhibition of the Hedgehog signaling pathway is a key mechanism by which veratramine acts.
- Veratramine demonstrates potential as a therapeutic agent for NSCLC treatment.
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