Document Detail

All-trans-retinoic acid induces cell growth arrest in a human medulloblastoma cell line.
MedLine Citation:
PMID:  17453147     Owner:  NLM     Status:  MEDLINE    
Medulloblastomas (MBs) are the most common malignant brain tumors of childhood. Antitumor agents promoting long-term survival with limited toxicities are thus far lacking. Preliminary findings suggest that retinoic acid (RA) derivatives (retinoids) exert antitumor effects by inhibiting cell proliferation and inducing cell differentiation, apoptosis, and growth arrest, and RAs have been specifically shown to induce apoptosis in some MB cells. However, there is no conclusive evidence of retinoids inducing cell growth arrest in MBs. The aim of this study is to investigate whether retinoids play a role in cell-cycle arrest of MB cells. All-trans-retinoic acid (ATRA) was selected for these studies as it is known to have the capacity of inducing cell cycle arrest and apoptosis in other types of cancer cells. Three MB cell lines (DAOY, D283 and D341) were subjected to ATRA treatment. The proportions of cells in the G0/G1 phase of cell cycle and in apoptosis were evaluated. The results showed that cell growth arrest, rather than apoptosis, was the main mechanism by which RA inhibited cell proliferation in the MB cell line DAOY, but not in the others (D283 and D341). Decreased expression of CyclinD1 and C-myc which regulate the transition of cell cycle was observed in DAOY cells following drug treatment, suggesting that these genes might be involved in ATRA retardation of cell cycle progression. Expression of RARbeta, a mediator of the action of retinoids, was also induced by RA in DAOY cells, implying that RAR-beta might also be involved in the mechanism of RA-induced cell cycle arrest. In conclusion, we have provided evidence for the first time that RA may induce cell cycle arrest in vitro in DAOY MB cells via inhibition of CyclinD1 or C-myc.
Qing Chang; Zhengshan Chen; Jiangfeng You; Michael A McNutt; Ting Zhang; Zhihui Han; Xiaoyan Zhang; Encong Gong; Jiang Gu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-24
Journal Detail:
Title:  Journal of neuro-oncology     Volume:  84     ISSN:  0167-594X     ISO Abbreviation:  J. Neurooncol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-10-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309335     Medline TA:  J Neurooncol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  263-7     Citation Subset:  IM    
Department of Pathology, School of Basic Medical Sciences, Peking (Beijing) University Health Science Center, 38 Xueyuan Road, Beijing, 100083, China.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cerebellar Neoplasms / metabolism*,  pathology
Cyclin D1 / drug effects
Medulloblastoma / metabolism*,  pathology
Proto-Oncogene Proteins c-myc / drug effects
Receptors, Retinoic Acid / drug effects
Reverse Transcriptase Polymerase Chain Reaction
Tretinoin / pharmacology*
Reg. No./Substance:
0/Antineoplastic Agents; 0/MYC protein, human; 0/Proto-Oncogene Proteins c-myc; 0/Receptors, Retinoic Acid; 0/retinoic acid receptor beta; 136601-57-5/Cyclin D1; 302-79-4/Tretinoin

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