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Anticancer Effects of Key Constituents of Pileostegia tomentella via ROS-Mediated Classical Apoptosis in Non-Small
Wen Zhong1, Leimin Jiang2, Bing Qing3
1International Zhuang Medicine Hospital affiliated to Guangxi University of Traditional Chinese Medicine; School of Zhuang Medicine, Guangxi University of Chinese Medicine; Guangxi Zhuang Autonomous Region Institute of Ethnic Medicine.
Abstract:
This study explores the anticancer potential of Pileostegia tomentella, with a particular focus on its ability to induce classical apoptosis in H1299 non-small cell lung cancer (NSCLC) cells through reactive oxygen species (ROS)-mediated pathways. Using a bioactivity-guided isolation approach, two active compounds, umbelliferone (UMB) and epi-Vogeloside, were identified as the major cytotoxic constituents. Both compounds exhibited significant inhibitory effects on cell viability and effectively triggered apoptotic cell death in H1299 cells. Mechanistic investigations demonstrated that treatment with UMB and epi-Vogeloside led to a marked increase in intracellular ROS levels, implicating oxidative stress as a key mediator. Western blot analysis revealed increased levels of cleaved caspase-3 and decreased expression of the anti-apoptotic protein Bcl-2, indicating activation of the intrinsic mitochondrial apoptotic pathway. Additionally, transcriptomic profiling showed widespread alterations in gene expression, further supporting disruption of cellular homeostasis. These results suggest that Pileostegia tomentella and its active constituents hold promise as potential therapeutic agents for lung cancer.
Insights
Pileostegia tomentella exhibits anticancer potential by inducing apoptosis in non-small cell lung cancer (NSCLC) cells. Its active compounds, umbelliferone and epi-Vogeloside, trigger cell death via reactive oxygen species (ROS) pathways.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
- The search for novel therapeutic agents from natural sources is crucial for developing new lung cancer treatments.
- Pileostegia tomentella is a plant with potential medicinal properties that warrants investigation for anticancer activity.
Purpose of the Study:
- To investigate the anticancer potential of Pileostegia tomentella extracts and isolated compounds against NSCLC cells.
- To elucidate the mechanism of action, focusing on apoptosis induction and the role of reactive oxygen species (ROS).
- To identify the specific cytotoxic constituents responsible for the observed anticancer effects.
Main Methods:
- Bioactivity-guided isolation was employed to identify active compounds from Pileostegia tomentella.
- In vitro assays were used to assess cell viability and apoptosis induction in H1299 NSCLC cells.
- Mechanistic studies involved measuring intracellular ROS levels, Western blot analysis for apoptosis markers (caspase-3, Bcl-2), and transcriptomic profiling.
Main Results:
- Two active compounds, umbelliferone (UMB) and epi-Vogeloside, were isolated and identified as major cytotoxic constituents.
- Both UMB and epi-Vogeloside significantly inhibited H1299 cell viability and induced apoptotic cell death.
- Treatment with these compounds increased intracellular ROS levels, activated caspase-3, decreased Bcl-2 expression, and altered gene expression profiles.
Conclusions:
- Pileostegia tomentella possesses significant anticancer properties against NSCLC.
- Umbelliferone and epi-Vogeloside are key cytotoxic compounds that induce apoptosis through ROS-mediated pathways.
- These findings suggest that Pileostegia tomentella and its constituents are promising candidates for novel lung cancer therapeutics.
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