Document Detail


Effects of carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone on the growth inhibition in human pulmonary adenocarcinoma Calu-6 cells.
MedLine Citation:
PMID:  19819288     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) is an uncoupler of mitochondrial oxidative phosphorylation in eukaryotic cells. Here, we evaluated the in vitro effects of FCCP on the growth of Calu-6 lung cancer cells. FCCP inhibited the growth of Calu-6 cells with an IC(50) of approximately 6.64+/-1.84 microM at 72 h, as shown by MTT. DNA flow cytometric analysis indicated that FCCP induced G1 phase arrest below 20 microM of FCCP. Treatment with FCCP decreased the level of CDKs and cyclines in relation to G1 phase. In addition, FCCP not only increased the p27 level but also enhanced its binding with CDK4, which was associated with hypophosphorylation of Rb protein. While transfection of p27 siRNA inhibited G1 phase arrest in FCCP-treated cells, it did not enhance Rb phosphorylation. FCCP also efficiently induced apoptosis. The apoptotic process was accompanied with an increase in sub-G1 cells, annexin V staining cells, mitochondria membrane potential (MMP) loss and cleavage of PARP protein. All of the caspase inhibitors (caspase-3, -8, -9 and pan-caspase inhibitor) markedly rescued the Calu-6 cells from FCCP-induced cell death. However, knock down of p27 protein intensified FCCP-induced cell death. Moreover, FCCP induced the depletion of GSH content in Calu-6 cells, which was prevented by all of the caspase inhibitors. In summary, our results demonstrated that FCCP inhibits the growth of Calu-6 cells in vitro. The growth inhibitory effect of FCCP might be mediated by cell cycle arrest and apoptosis via decrease of CDKs and caspase activation, respectively. These findings now provide a better elucidation of the mechanisms involved in FCCP-induced growth inhibition in lung cancer.
Authors:
Yong Hwan Han; Hwa Jin Moon; Bo Ra You; Sung Zoo Kim; Suhn Hee Kim; Woo Hyun Park
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-09
Journal Detail:
Title:  Toxicology     Volume:  265     ISSN:  1879-3185     ISO Abbreviation:  Toxicology     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-17     Completed Date:  2009-12-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  101-7     Citation Subset:  IM    
Affiliation:
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju 561-180, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy*,  pathology
Annexin A5 / metabolism
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Cyclin-Dependent Kinases / metabolism
DNA, Neoplasm / drug effects
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Formazans / metabolism
G1 Phase / drug effects
Humans
Inhibitory Concentration 50
Lung Neoplasms / drug therapy*,  pathology
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects
Mitochondrial Membranes / drug effects
Tetrazolium Salts / metabolism
Time Factors
Uncoupling Agents / pharmacology*
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Antineoplastic Agents; 0/DNA, Neoplasm; 0/Formazans; 0/Tetrazolium Salts; 0/Uncoupling Agents; 23305-68-2/MTT formazan; 370-86-5/Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; EC 2.7.11.22/Cyclin-Dependent Kinases

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


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