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α-Viniferin-Induced Apoptosis through Downregulation of SIRT1 in Non-Small Cell Lung Cancer Cells
Cheng Huang1, Zi-Jun Lin2,3, Jui-Chieh Chen4
1Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
Abstract:
α-Viniferin, a natural stilbene compound found in plants and a polymer of resveratrol, had demonstrated potential anti-cancer and anti-inflammatory effects. However, the specific mechanisms underlying its anti-cancer activity were not yet fully understood and required further investigation. This study evaluated the effectiveness of α-viniferin and ε-viniferin using MTT assay. Results showed that α-viniferin was more effective than ε-viniferin in reducing the viability of NCI-H460 cells, a type of non-small cell lung cancer. Annexin V/7AAD assay results provided further evidence that the decrease in cell viability observed in response to α-viniferin treatment was due to the induction of apoptosis in NCI-H460 cells. The present findings indicated that treatment with α-viniferin could stimulate apoptosis in cells by cleaving caspase 3 and PARP. Moreover, the treatment reduced the expression of SIRT1, vimentin, and phosphorylated AKT, and also induced AIF nuclear translocation. Furthermore, this research provided additional evidence for the effectiveness of α-viniferin as an anti-tumor agent in nude mice with NCI-H460 cell xenografts. As demonstrated by the TUNEL assay results, α-viniferin promoted apoptosis in NCI-H460 cells in nude mice.
Insights
Alpha-viniferin effectively combats non-small cell lung cancer by inducing apoptosis in NCI-H460 cells. This natural compound shows significant anti-tumor effects, offering potential for new lung cancer treatments.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Alpha-viniferin, a stilbene polymer, exhibits potential anti-cancer properties.
- The precise anti-cancer mechanisms of alpha-viniferin require further elucidation.
- Non-small cell lung cancer (NCSC) remains a significant global health challenge.
Purpose of the Study:
- To investigate the anti-cancer efficacy of alpha-viniferin and epsilon-viniferin against NCI-H460 non-small cell lung cancer cells.
- To elucidate the molecular mechanisms underlying alpha-viniferin's anti-cancer activity.
- To evaluate the in vivo anti-tumor effects of alpha-viniferin.
Main Methods:
- MTT assay to assess cell viability.
- Annexin V/7AAD and TUNEL assays to detect apoptosis.
- Western blotting to analyze protein expression (caspase 3, PARP, SIRT1, vimentin, p-AKT).
- In vivo xenograft model in nude mice.
Main Results:
- Alpha-viniferin significantly reduced NCI-H460 cell viability, outperforming epsilon-viniferin.
- Alpha-viniferin induced apoptosis in NCI-H460 cells, evidenced by caspase 3 and PARP cleavage, and AIF nuclear translocation.
- Treatment with alpha-viniferin decreased SIRT1, vimentin, and phosphorylated AKT expression.
- In vivo studies confirmed alpha-viniferin's anti-tumor efficacy by promoting apoptosis in xenograft models.
Conclusions:
- Alpha-viniferin demonstrates potent anti-cancer activity against non-small cell lung cancer by inducing apoptosis.
- The compound modulates key apoptotic and signaling pathways, including caspase activation and SIRT1/AKT inhibition.
- Alpha-viniferin represents a promising therapeutic candidate for non-small cell lung cancer treatment.
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