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CDKN1A Gene Expression in Two Multiple Myeloma Cell Lines With Different P53 Functionality
DH. Drozdkova, J. Gursky, J. Minarik, I. Überall, Z. Kolar, KS. Trtkova,
Language English Country Greece
Document type Comparative Study, Journal Article
NLK
Free Medical Journals
from 2004 to 2 years ago
Open Access Digital Library
from 2004-01-01
- MeSH
- Apoptosis drug effects MeSH
- Cyclin-Dependent Kinase Inhibitor p21 antagonists & inhibitors genetics MeSH
- Histone Deacetylase Inhibitors pharmacology MeSH
- Cell Cycle Checkpoints drug effects MeSH
- Hydroxamic Acids pharmacology MeSH
- Humans MeSH
- Multiple Myeloma drug therapy genetics metabolism pathology MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- Antineoplastic Agents pharmacology MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
BACKGROUND/AIM: Multiple myeloma is a highly heterogeneous disease of clonal plasma cells. Histone deacetylase (HDAC) inhibitors are promising anticancer drugs but their precise mechanisms of actions are not well understood. MATERIALS AND METHODS: Cell-cycle regulation and pro-apoptotic effects of two histone deacetylase inhibitors, suberohydroxamic acid (SAHA) and suberoylanilide hydroxamic acid (SBHA), were analyzed in multiple myeloma cell lines RPMI8226 and U266 with differing TP53 status using gene-expression analysis. RESULTS: Enhanced expression of cyclin-dependent kinase inhibitor 1A (CDKN1A/p21WAF/CIP1) detected in the TP53-deleted U266 cell line after SAHA treatment indicates the P53-independent mode of transcriptional activation of CDKN1A gene. In contrast, CDKN1A gene expression was significantly increased by both SBHA and SAHA treatment of TP53-mutated RPMI8226 cells. CONCLUSION: SAHA appears to be a potentially effective pro-apoptotic and anticancer drug with universal application in the treatment of heterogeneous populations of multiple myeloma cells.
References provided by Crossref.org
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- $a Drozdkova, Denisa Hrckova $u Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic denisa.drozdkova@seznam.cz katerina.smesny@upol.cz. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
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- $a BACKGROUND/AIM: Multiple myeloma is a highly heterogeneous disease of clonal plasma cells. Histone deacetylase (HDAC) inhibitors are promising anticancer drugs but their precise mechanisms of actions are not well understood. MATERIALS AND METHODS: Cell-cycle regulation and pro-apoptotic effects of two histone deacetylase inhibitors, suberohydroxamic acid (SAHA) and suberoylanilide hydroxamic acid (SBHA), were analyzed in multiple myeloma cell lines RPMI8226 and U266 with differing TP53 status using gene-expression analysis. RESULTS: Enhanced expression of cyclin-dependent kinase inhibitor 1A (CDKN1A/p21WAF/CIP1) detected in the TP53-deleted U266 cell line after SAHA treatment indicates the P53-independent mode of transcriptional activation of CDKN1A gene. In contrast, CDKN1A gene expression was significantly increased by both SBHA and SAHA treatment of TP53-mutated RPMI8226 cells. CONCLUSION: SAHA appears to be a potentially effective pro-apoptotic and anticancer drug with universal application in the treatment of heterogeneous populations of multiple myeloma cells.
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