Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7α and HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549
| Autor: | Yang Bai, Xiao-hua Wang, Xin-mei Chen, Xiao‑Lin Xie, Han-wu Long, Yu-yin Yang, Qiang Jia, Yu-jian Zhong, Shi-gen Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
F-Box-WD Repeat-Containing Protein 7
Lung Neoplasms Cell Survival Ubiquitin-Protein Ligases Histone Deacetylase 2 lcsh:Medicine Adenocarcinoma of Lung Apoptosis Cell Cycle Proteins Histone Deacetylase 1 Biology Adenocarcinoma Proto-Oncogene Proteins c-myc chemistry.chemical_compound Glycogen Synthase Kinase 3 Wogonin Cell Line Tumor MG132 Humans RNA Messenger lcsh:Science S-Phase Kinase-Associated Proteins Cell Proliferation A549 cell Membrane Potential Mitochondrial Multidisciplinary Glycogen Synthase Kinase 3 beta Cell growth F-Box Proteins Cell Cycle lcsh:R Cell cycle XIAP Gene Expression Regulation Neoplastic chemistry Flavanones Cancer research lcsh:Q Signal transduction Research Article Signal Transduction |
| Zdroj: | PLoS ONE, Vol 8, Iss 11, p e79201 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Wogonin is a plant monoflavonoid which has been reported to inhibit cell growth and/or induce apoptosis in various tumors. The present study examined the apoptosis-inducing activity and underlying mechanism of action of wogonin in A549 cells. The results showed that wogonin was a potent inhibitor of the viability of A549 cells. Apoptotic protein changes detected after exposure to wogonin included decreased XIAP and Mcl-1 expression, increased cleaved-PARP expression and increased release of AIF and cytotchrome C. Western blot analysis showed that the activity of c-Myc/Skp2 and HDAC1/HDAC2 pathways, which play important roles in tumor progress, was decreased. Quantitative PCR identified increased levels of c-Myc mRNA and decreased levels of its protein. Protein levels of Fbw7α, GSK3β and Thr58-Myc, which are involved in c-Myc ubiquitin-dependent degradation, were also analyzed. After exposure to wogonin, Fbw7α and GSK3β expression decreased and Thr58-Myc expression increased. However, MG132 was unable to prevent c-Myc degradation. The present results suggest that wogonin has multiple anti-cancer effects associated with degradation of c-Myc, SKP2, HDAC1 and HDAC2. Its ability to induce apoptosis independently of Fbw7α suggests a possible use in drug-resistance cancer related to Fbw7 deficiency. Further studies are needed to determine which pathways are related to c-Myc and Fbw7α reversal and whether Thr58 phosphorylation of c-Myc is dependent on GSK3β. |
| Databáze: | OpenAIRE |
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