Document Detail


Paclitaxel induced apoptosis in breast cancer cells requires cell cycle transit but not Cdc2 activity.
MedLine Citation:
PMID:  16972069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Paclitaxel (PTX) is a widely used chemotherapy agent and may cause cell death by apoptosis subsequent to microtubule (MT) disruption. In this paper, we have investigated whether cell cycle transit and or Cdc2 (Cdk1) activity is required for the apoptosis induced by PTX.
METHODS: Cell cycle was analyzed by flow cytometry, Cdc2 was assayed bio chemically. Cdc2 activity was decreased by siRNA and dominant negative (dn) Cdc2 expression. Cells were arrested by chemical or biological inhibitors in a G1 or S phase. Apoptosis was measured by DNA fragmentation and examination of nuclei by microscopy. JNK and AKT activations were assessed as well.
RESULTS: Cell cycle inhibition was highly effective in decreasing PTX induced apoptosis. MT morphology was not altered by these inhibitors. PTX induced JNK activity or AKT mediated BAD phosphorylation was unaffected by cell cycle inhibitors. Abrogation of Cdc 2 activity was without effect on PTX induced apoptosis.
CONCLUSIONS: While cell cycle transit is required for PTX induced apoptosis; Cdc2 activity is not required.
Authors:
D Henley; M Isbill; R Fernando; J S Foster; J Wimalasena
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-09-14
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  59     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2006-11-30     Completed Date:  2007-04-23     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  235-49     Citation Subset:  IM    
Affiliation:
Department of OB/GYN, GSM, UTMCK, University of Tennessee, Alcoa Highway, Knoxville, TN 37920, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology
Apoptosis / drug effects*
Blotting, Western
Breast Neoplasms / metabolism,  pathology,  physiopathology
CDC2 Protein Kinase / genetics,  metabolism*
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Nucleus / drug effects,  metabolism
Cell Survival / drug effects
DNA Fragmentation / drug effects
Estradiol / analogs & derivatives,  pharmacology
Flow Cytometry
Humans
Hydroxyurea / pharmacology
Inhibitor of Apoptosis Proteins
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Microtubule-Associated Proteins / metabolism
Microtubules / drug effects
Mitotic Spindle Apparatus / drug effects,  metabolism
Neoplasm Proteins / metabolism
Paclitaxel / pharmacology*
Purines / pharmacology
RNA, Small Interfering / genetics
Thymidine / pharmacology
Transfection
bcl-Associated Death Protein / metabolism
Grant Support
ID/Acronym/Agency:
CA 84048/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/BAD protein, human; 0/BIRC5 protein, human; 0/Inhibitor of Apoptosis Proteins; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Purines; 0/RNA, Small Interfering; 0/bcl-Associated Death Protein; 0/roscovitine; 127-07-1/Hydroxyurea; 22X328QOC4/fulvestrant; 33069-62-4/Paclitaxel; 50-28-2/Estradiol; 50-89-5/Thymidine; EC 2.7.11.22/CDC2 Protein Kinase; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases

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


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