Document Detail


Abrogation of G2 checkpoint specifically sensitize p53 defective cells to cancer chemotherapeutic agents.
MedLine Citation:
PMID:  11299740     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Chkl is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates Cdc25C at the late G2 phase. The inactivation of Cdc25C and consequently, the inactivation of Cdc2, are required for the G2 arrest induced by DNA damage.
METHODS: We treated 184B5 cell line and its E6 transformed cell lines with adriamycin in the presence of staurosporine or UCNO1 and examined G2 arrest and cell death.
RESULTS: We found that adriamycin induced a p53 and p21 response as well as a G1 arrest in 184B5 cells, but not in its E6 transformed cells. Staurosporine or UCNO1 abrogated the G2 arrest induced by adriamycin in both cell lines. In addition, staurosporine or UCNO1 specifically sensitized p53 incompetent cells to adriamycin.
CONCLUSION: G2/M checkpoint abrogators can potentially enhance the cytotoxic effect of conventional chemotherapeutic reagents specifically to tumor cells.
Authors:
Y Luo; S K Rockow-Magnone; M K Joseph; J Bradner; C C Butler; S K Tahir; E K Han; S C Ng; J M Severin; E J Gubbins; R M Reilly; A Rueter; R L Simmer; T F Holzman; V L Giranda
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  21     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2001 Jan-Feb
Date Detail:
Created Date:  2001-04-12     Completed Date:  2001-05-03     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  23-8     Citation Subset:  IM    
Affiliation:
Department 47S AP9A, Cancer Research, Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA.
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / pharmacology
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Transformed
DNA Damage / drug effects*
Doxorubicin / pharmacology*
Enzyme Inhibitors / pharmacology
G2 Phase
Humans
Neoplasms / metabolism,  pathology*
Protein Kinases / metabolism
Staurosporine / pharmacology
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism*
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Tumor Suppressor Protein p53; 23214-92-8/Doxorubicin; 62996-74-1/Staurosporine; 7BU5H4V94A/7-hydroxystaurosporine; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Checkpoint kinase 1

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


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