| FK228 and oncogenic H-Ras synergistically induce Mek1/2 and Nox-1 to generate reactive oxygen species for differential cell death. | |
| | |
MedLine Citation:
|
PMID: 20700043 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
To investigate the mechanism behind the pro-apoptotic ability of oncogenic H-Ras to enhance FK228-induced apoptosis, we primarily used the 10T1/2-TR-H-Ras cell line, in which ectopic expression of oncogenic H-Ras(V12) is controlled by the addition of tetracycline into cultures, and secondarily used oncogenic H-Ras-expressing MCF10A cells in our studies. Our results showed the pro-apoptotic roles of Mek1/2 activation, nicotinamide adenine dinucleotide phosphate-oxidase 1 (Nox-1) elevation, and reactive oxygen species (ROS) production in FK228-induced selective cell death of oncogenic H-Ras-expressing cells versus counterpart cells. We found that although Nox-1 elevation and ROS production played essential roles in oncogenic H-Ras-induced cell proliferation and morphological transformation, the expression of oncogenic H-Ras and FK228 treatment synergistically induced activation of Mek1/2. This activation resulted in differentially increased Nox-1 elevation and ROS production leading to selective cell death of oncogenic H-Ras-expressing cells versus counterpart cells. We also found that FK228 treatment induced mitochondrial ROS and Mek1/2 activation, bypassing Raf-1, to downstream Erk1/2, participating in the induction of selective cell death. Thus, the pro-apoptotic abilities of Mek1/2 and Nox-1 should be considered as potential targets in designing therapeutic protocols using FK228 to assure ROS-mediated cell death for treating cancer cells acquiring Ras activation. |
| | |
Authors:
|
Shambhunath Choudhary; Kusum Rathore; Hwa-Chain Robert Wang |
Related Documents
:
|
18426973 - The peroxisome: a production in four acts. 8764563 - Il-8/nap-1 is the major t-cell chemoattractant in synovial tissues of rheumatoid arthri... 3510993 - Cell cycle analysis using flow cytometry. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Anti-cancer drugs Volume: 21 ISSN: 1473-5741 ISO Abbreviation: Anticancer Drugs Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-09-02 Completed Date: 2010-12-22 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: England |
Other Details:
|
Languages: eng Pagination: 831-40 Citation Subset: IM |
Affiliation:
|
Department of Comparative Medicine, The University of Tennessee, Knoxville, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antibiotics, Antineoplastic / pharmacology* Apoptosis / drug effects Cell Proliferation Cells, Cultured Depsipeptides / pharmacology* Gene Expression Regulation / drug effects Humans MAP Kinase Kinase 1 / metabolism MAP Kinase Kinase 2 / metabolism Mice NADH, NADPH Oxidoreductases / metabolism* Proto-Oncogene Proteins p21(ras) / metabolism Reactive Oxygen Species / metabolism* Tetracycline / pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Antibiotics, Antineoplastic; 0/Depsipeptides; 0/Reactive Oxygen Species; 128517-07-7/romidepsin; 60-54-8/Tetracycline; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.99.-/NADPH oxidase 1; EC 2.7.12.2/MAP Kinase Kinase 1; EC 2.7.12.2/MAP Kinase Kinase 2; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Novel Oral Anticoagulants: Implications in the Perioperative Setting.
Next Document: Anti-EMMPRIN antibody treatment of head and neck squamous cell carcinoma in an ex-vivo model.