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Published on: December 30, 2025
Expression proteomics to p53 mutation reactivation with PRIMA-1 in breast cancer cells
Kyunghee Lee1, Tao Wang, Andrzej J Paszczynski
1Department of Pharmaceutical Sciences, Washington State University, 259 Wegner Hall, Pullman, WA 99164-6534, USA.
Abstract:
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.
Insights
PRIMA-1 reactivates mutant p53, inducing apoptosis in breast cancer cells. This study identified key proteins involved in glycolysis and mitochondrial pathways activated by PRIMA-1, offering new therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Research
- Proteomics
Background:
- Mutant p53 protein is frequently found in various cancers, including breast cancer.
- PRIMA-1 is a small molecule drug that can restore wild-type function to mutant p53.
- Understanding the molecular mechanisms of PRIMA-1-induced apoptosis is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To identify molecular targets involved in PRIMA-1-induced apoptosis in breast cancer cells.
- To elucidate the role of glycolysis and mitochondrial pathways in PRIMA-1's anti-cancer effects.
Main Methods:
- Proteomics approach using two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry.
- Comparative proteomic analysis of PRIMA-1-treated MDA-231 (mutant p53) and MCF-7 (wild-type p53) breast carcinoma cells.
- Assays to detect cytochrome c release and caspase-3 activation.
Main Results:
- Seven proteins were upregulated exclusively in PRIMA-1-treated MDA-231 cells.
- These proteins are associated with anaerobic glycolysis and the mitochondrial intrinsic apoptosis pathway.
- PRIMA-1 treatment led to cytochrome c release and caspase-3 activation in MDA-231 cells.
Conclusions:
- PRIMA-1-induced apoptosis in breast cancer cells with mutant p53 involves the upregulation of glycolysis-related proteins.
- The study highlights the activation of the mitochondrial intrinsic apoptosis pathway, linked to glycolysis, as a key mechanism of PRIMA-1.
- These findings suggest PRIMA-1 as a promising therapeutic agent for p53-mutated breast cancers.
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