Document Detail

Antiproliferative activity of cisplatin detected by CFSE in p53-proficient and p53-deficient cells.
MedLine Citation:
PMID:  18161532     Owner:  NLM     Status:  MEDLINE    
We have previously developed experimental and data analysis procedures to measure the antiproliferative activity of drugs in continuously proliferating cancer cell lines using carboxyfluorescein diacetate succinimidyl ester (CFSE). The method was applied here to analyze the role of p53 in the effect of the anticancer drug cisplatin, distinguishing events occurring in the first generation of cells from those in the second and subsequent generations. A CFSE-loaded colon carcinoma cell line expressing functional wild-type p53 was treated for 1 with cisplatin in parallel with its p53-deficient counterpart, collecting frequency distributions of DNA and CFSE content up to 72 h after treatment. At a sublethal cisplatin concentration proliferation was temporarily inhibited but then the block was overcome and most cells were able to divide several times. The initial block was stronger in HCTp53-/- cells, resulting in a larger proportion of undivided cells at 24 h. This was confirmed and amplified at a higher, lethal concentration, where undivided G(2)M-blocked p53-deficient cells eventually died by non-apoptotic mechanisms, while p53-proficient cells avoided this with a less stringent block. This gave p53-proficient cells more time to repair and eventually decide on survival or apoptotic death before traversing the cycle into their second generation.
Paolo Ubezio; Monica Lupi; Giada Matera
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunological investigations     Volume:  36     ISSN:  1532-4311     ISO Abbreviation:  Immunol. Invest.     Publication Date:  2007  
Date Detail:
Created Date:  2007-12-28     Completed Date:  2008-03-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8504629     Medline TA:  Immunol Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  847-59     Citation Subset:  IM    
Biophysics Unit, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
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MeSH Terms
Cisplatin / pharmacology*
Fluoresceins / diagnostic use*,  metabolism
Fluorometry / methods*
Genes, p53 / drug effects,  immunology
Succinimides / diagnostic use,  metabolism*
Tumor Suppressor Protein p53
Reg. No./Substance:
0/5-(6)-carboxyfluorescein diacetate succinimidyl ester; 0/Fluoresceins; 0/Succinimides; 0/Tumor Suppressor Protein p53; 15663-27-1/Cisplatin

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