Document Detail


Perifosine induces cell apoptosis in human osteosarcoma cells: new implication for osteosarcoma therapy?
MedLine Citation:
PMID:  23015227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Despite the advances of adjuvant chemotherapy and significant improvement of survival, the prognosis for patients with osteosarcoma is generally poor. The search for more effective anti-osteosarcoma agents is necessary and urgent. Here we report that perifosine induces cell apoptosis and growth inhibition in cultured human osteosarcoma cells. Perifosine blocks Akt/mTOR complex 1 (mTORC1) signaling, while promoting caspase-3, c-Jun N-terminal kinases (JNK), and p53 activation. Further, perifosine inhibits survivin expression probably by disrupting its association with heat shock protein-90 (HSP-90). These signaling changes together were responsible for a marked increase of osteosarcoma cell apoptosis and growth inhibition. Finally, we found that a low dose of perifosine enhanced etoposide- or doxorubicin-induced anti-OS cells activity. The results together suggest that perifosine might be used as a novel and effective anti-osteosarcoma agent.
Authors:
Chen Yao; Jian-jun Wei; Zu-yu Wang; Hui-min Ding; Dong Li; Shi-chang Yan; Yong-jiang Yang; Zhang-ping Gu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell biochemistry and biophysics     Volume:  65     ISSN:  1559-0283     ISO Abbreviation:  Cell Biochem. Biophys.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-19     Completed Date:  2013-08-27     Revised Date:  2013-09-30    
Medline Journal Info:
Nlm Unique ID:  9701934     Medline TA:  Cell Biochem Biophys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  217-27     Citation Subset:  IM    
Affiliation:
Department of Orthopedics, BenQ Medical Center, Nanjing Medical University, Nanjing, Jiangsu, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
Apoptosis / drug effects*
Blotting, Western
Caspase 3 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects*
Cell Survival / drug effects
Dose-Response Relationship, Drug
Doxorubicin / pharmacology
Drug Synergism
Enzyme-Linked Immunosorbent Assay
Etoposide / pharmacology
Humans
JNK Mitogen-Activated Protein Kinases / metabolism
Multiprotein Complexes / metabolism
Osteosarcoma / drug therapy,  metabolism,  pathology
Phosphorylcholine / analogs & derivatives*,  pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / drug effects
TOR Serine-Threonine Kinases / metabolism
Tumor Suppressor Protein p53 / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Multiprotein Complexes; 0/Tumor Suppressor Protein p53; 0/mechanistic target of rapamycin complex 1; 107-73-3/Phosphorylcholine; 23214-92-8/Doxorubicin; 2GWV496552/perifosine; 33419-42-0/Etoposide; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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