|Paclitaxel induced apoptosis in breast cancer cells requires cell cycle transit but not Cdc2 activity.|
|PMID: 16972069 Owner: NLM Status: MEDLINE|
|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.
|D Henley; M Isbill; R Fernando; J S Foster; J Wimalasena|
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|Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-09-14|
|Title: Cancer chemotherapy and pharmacology Volume: 59 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2007 Feb|
|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|
|Languages: eng Pagination: 235-49 Citation Subset: IM|
|Department of OB/GYN, GSM, UTMCK, University of Tennessee, Alcoa Highway, Knoxville, TN 37920, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Antineoplastic Agents, Phytogenic
Apoptosis / drug effects*
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
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
bcl-Associated Death Protein / metabolism
|CA 84048/CA/NCI NIH HHS|
|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 18.104.22.168/CDC2 Protein Kinase; EC 22.214.171.124/JNK Mitogen-Activated Protein Kinases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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