Document Detail

Induction of PUMA-alpha and down-regulation of PUMA-beta expression is associated with benzo(a)pyrene-induced apoptosis in MCF-7 cells.
MedLine Citation:
PMID:  19397966     Owner:  NLM     Status:  MEDLINE    
Benzo(a)pyrene (BP) forms benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adducts in human breast adenocarcinoma MCF-7 cells, leading to p53 protein induction and phosphorylation. Although BP-induced apoptosis in rodent cells is known, it is still unclear in human cells. Here we have analyzed the effects of BP on p53 related apoptotic proteins, cell cycle and cell death in MCF-7 cells. PUMA-protein (p53 up-regulated modulator of apoptosis) levels were changed after BP exposure so that PUMA-alpha protein was statistically significantly increased whereas PUMA-beta protein was statistically significantly decreased. PUMA-protein levels were also investigated in ZR-75-1 cells, where PUMA-alpha protein was statistically significantly increased. Cytochrome c, which is released from mitochondria during apoptosis to form the apoptosome, was increased in cytoplasmic fraction after BP exposure in MCF-7 cells. Increased apoptosis was also seen after 48 and 72 h BP exposure (2.5 and 5 microM). In addition, BP decreased dose dependently cell viability (2.5 and 5 microM) and increased ROS formation (1 and 10 microM). Our results suggest that PUMA-alpha protein is involved in BP-induced cell death most likely through a p53 dependent apoptotic pathway.
Marjo Tampio; Piia Markkanen; Katja A Puttonen; Eveliina Hagelberg; Hannu Heikkinen; Kati Huhtinen; Jarkko Loikkanen; Maija-Riitta Hirvonen; Kirsi H Vähäkangas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-03
Journal Detail:
Title:  Toxicology letters     Volume:  188     ISSN:  1879-3169     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-15     Completed Date:  2009-07-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  214-22     Citation Subset:  IM    
University of Kuopio, Department of Pharmacology and Toxicology, Yliopistonranta 1C, Kuopio, Finland.
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MeSH Terms
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / biosynthesis*
Benzo(a)pyrene / toxicity*
Cell Line, Tumor
Cytochromes c / metabolism
Cytosol / drug effects,  metabolism
Flow Cytometry
Membrane Potentials / drug effects
Microscopy, Confocal
Mitochondria / drug effects,  metabolism
Protein Isoforms
Proto-Oncogene Proteins / biosynthesis*
Reactive Oxygen Species / metabolism
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BBC3 protein, human; 0/Protein Isoforms; 0/Proto-Oncogene Proteins; 0/Reactive Oxygen Species; 50-32-8/Benzo(a)pyrene; 9007-43-6/Cytochromes c

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