Role of p53, PUMA, and Bax in wogonin-induced apoptosis in human cancer cells
| Autor: | Clifford Kim, Yong J. Lee, Dae Hee Lee, Lin Zhang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Programmed cell death Cell Survival Apoptosis Caspase 3 DNA Fragmentation Biochemistry Article chemistry.chemical_compound Bcl-2-associated X protein Wogonin Cell Line Tumor Proto-Oncogene Proteins hemic and lymphatic diseases Puma LNCaP Humans Cells Cultured bcl-2-Associated X Protein Flavonoids Pharmacology biology Prostate Cytochromes c Epithelial Cells biology.organism_classification Caspase 9 Gene Expression Regulation chemistry Flavanones Cancer cell Cancer research biology.protein Tumor Suppressor Protein p53 biological phenomena cell phenomena and immunity Apoptosis Regulatory Proteins |
| Zdroj: | Biochemical Pharmacology. 75:2020-2033 |
| ISSN: | 0006-2952 |
| Popis: | We observed that treatment of prostate cancer cells for 24 h with wogonin, a naturally occurring monoflavonoid, induced cell death in a dose- and time-dependent manner. Exposure of wogonin to LNCaP cells was associated with increased intracellular levels of p21(Cip-1), p27(Kip-1), p53, and PUMA, oligomerization of Bax, release of cytochrome c from the mitochondria, and activation of caspases. We also confirmed the role of p53 by noting that knock-in in p53 expression by transfecting p53 DNA increased wogonin-induced apoptosis in p53-null PC-3 cells. To study the mechanism of PUMA up-regulation, we determined the activities of PUMA promoter in the wogonin treated and untreated cells. Increase of the intracellular levels of PUMA protein was due to increase in transcriptional activity. Data from chromatin immunoprecipitation (ChIP) analyses revealed that wogonin activated the transcription factor p53 binding activity to the PUMA promoter region. We observed that the up-regulation of PUMA mediated wogonin cytotoxicity. Further characterization of the transcriptional response to wogonin in HCT116 human colon cancer cells demonstrated that PUMA induction was p53-dependent; deficiency in either p53 or PUMA significantly protected HCT116 cells against wogonin-induced apoptosis. Also, wogonin promoted mitochondrial translocation and multimerization of Bax. Interestingly, wogonin (100 microM) treatment did not affect the viability of normal human prostate epithelial cells (PrEC). Taken together, these results indicate that p53-dependent transcriptional induction of PUMA and oligomerization of Bax play important roles in the sensitivity of cancer cells to apoptosis induced by caspase activation through wogonin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect