| Additive effects of C(2)-ceramide on paclitaxel-induced premature senescence of human lung cancer cells. | |
| | |
MedLine Citation:
|
PMID: 20624405 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
AIMS: the aims of the study are to investigate the additive effect of exogenous short-carbon chain phospholipids, C(2)-ceramide, on an anti-cancer drug paclitaxel (PTX)-induced senescence of human non-small cell lung cancer (NSCLC) cells deficient in functional p53 and p16, and to examine whether mitogen-activated protein kinase (MAPK) plays a role in ceramide-sensitized senescence of NSCLC cells. MAIN METHODS: to determine whether exogenous C(2)-ceramide renders lung cancer cells more sensitive to PTX treatment, techniques employing a flow cytometry-based cell cycle analysis and acidic β-galactosidase staining for senescent cells were used. Furthermore, to elucidate the role of MAPK proteins in modulating senescence, assays for protein levels of selective MAPKs and Bcl-2 family members, and detection of transcriptional levels senescence-associated genes were used in the study. KEY FINDINGS: a sub-lethal dose of C(2)-ceramide sensitized the NSCLC H1299 cells to PTX treatment. The additive effects of C(2)-ceramide and PTX resulted in proliferative inhibition, G(2)-phase arrest of cell cycle, activation of p38 and eventually premature senescence. Importantly, neither p53, p21(waf1/cip1) nor p16(ink4) was shown to be involved in C(2)-ceramide-sensitized proliferative inhibition and senescence of H1299 cells by PTX in our study. SIGNIFICANCE: our study demonstrates that the short-carbon chain C(2)-ceramide can effectively sensitize PTX-induced senescence of H1299 cells via both p21(waf1/cip1)- and p16(ink4)-independent pathways. |
| | |
Authors:
|
Jeff Yi-Fu Chen; Chi-Ching Hwang; Wei-Yi Chen; Jing-Ching Lee; Tzu-Fun Fu; Kang Fang; Ying-Chieh Chu; Ya-Lan Huang; Jia-Cheng Lin; Wen-Hui Tsai; Hsueh-Wei Chang; Bing-Hung Chen; Chien-Chih Chiu |
Related Documents
:
|
19440315 - Diminished telomeric 3' overhangs are associated with telomere dysfunction in hoyeraal-... 17055735 - Age-related changes of cell outgrowth from rat calvarial and mandibular bone in vitro. 3173685 - Morphometrical and microdensitometrical studies on phenylethanolamine-n-methyltransfera... 20939035 - New biomarkers probing depth of cell senescence assessed by laser scanning cytometry. 12612135 - Oxidative folding of interleukin-2 is impaired in flavin-deficient jurkat cells, causin... 1325445 - Regulatory volume decrease in the presence of hco3- by single osteosarcoma cells umr-10... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-17 |
Journal Detail:
|
Title: Life sciences Volume: 87 ISSN: 1879-0631 ISO Abbreviation: Life Sci. Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-09-10 Completed Date: 2010-11-04 Revised Date: 2011-11-10 |
Medline Journal Info:
|
Nlm Unique ID: 0375521 Medline TA: Life Sci Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 350-7 Citation Subset: IM |
Copyright Information:
|
2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Biotechnology, Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Apoptosis
/
drug effects Carcinoma, Non-Small-Cell Lung / drug therapy*, metabolism, pathology* Caspase 3 / metabolism Cell Aging / drug effects* Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects, genetics Cyclin-Dependent Kinase Inhibitor p21 / genetics DNA Fragmentation / drug effects Extracellular Signal-Regulated MAP Kinases / metabolism G2 Phase / drug effects GTP-Binding Proteins / genetics Gene Expression / drug effects, genetics Humans Inhibitor of Apoptosis Proteins / genetics JNK Mitogen-Activated Protein Kinases / metabolism Microfilament Proteins / genetics Muscle Proteins / genetics Osteonectin / genetics Paclitaxel / pharmacology* Phosphorylation / drug effects Plasminogen Activator Inhibitor 1 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism Sphingosine / analogs & derivatives*, pharmacology Transglutaminases / genetics beta-Galactosidase / metabolism p38 Mitogen-Activated Protein Kinases / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/BIRC3 protein, human; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Inhibitor of Apoptosis Proteins; 0/Microfilament Proteins; 0/Muscle Proteins; 0/N-acetylsphingosine; 0/Osteonectin; 0/Plasminogen Activator Inhibitor 1; 0/Proto-Oncogene Proteins c-bcl-2; 0/SERPINE1 protein, human; 0/transgelin; 123-78-4/Sphingosine; 33069-62-4/Paclitaxel; EC 2.3.2.-/transglutaminase 2; EC 2.3.2.13/Transglutaminases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.2.1.23/beta-Galactosidase; EC 3.4.22.-/Caspase 3; EC 3.6.1.-/GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10 melanoma...
Next Document: Preferential adhesion of leukocytes near bifurcations is endothelium independent.