Expression proteomics to p53 mutation reactivation with PRIMA-1 in breast cancer cells.
PRIMA-1 has emerged as a small molecule that restores the wild type function to mutant p53. To identify molecular targets that are involved in PRIMA-1-induced apoptosis, we used a proteomics approach with two-dimensional gel electrophoresis coupled with liquid chromatography-tandem mass spectrometry for protein identification. By comparing the proteome of the PRIMA-1-treated MDA-231 breast carcinoma cells with that of MCF-7 cells, we have identified seven proteins that upregulated only in MDA-231 cells as a result of PRIMA-1-induced apoptosis. The identified proteins are involved in anaerobic glycolysis and in mitochondrial intrinsic apoptosis. Treatment of MDA-231 cells with PRIMA-1 resulted in the release of mitochondrial cytochrome c as well as the activation of caspase-3, which are essential for the execution of apoptosis. We present evidence to suggest that PRIMA-1-induced apoptosis in breast cancer cells with mutated p53 function involved the expression of proteins required for the activation of mitochondrial intrinsic pathway that is glycolysis-relevant.
Lee
Kyunghee
K
Department of Pharmaceutical Sciences, Washington State University, 259 Wegner Hall, Pullman, WA 99164-6534, USA.
Wang
Tao
T
Paszczynski
Andrzej J
AJ
Daoud
Sayed S
SS
D001372:Aza Compounds / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D040901:Proteomics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016159:Tumor Suppressor Protein p53; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C451219:2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one