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Comparative pharmacoproteomics reveals potential targets for berberine, a promising therapy for colorectal cancer
Mingfu Tong1, Haiming Liu2, Jianyu Hao1
1Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Abstract:
Berberine (BBR), a natural isoquinoline alkaloid, has been shown to be a promising therapeutic agent for colorectal cancer (CRC), but the molecular mechanism remains unclear. Here, we used mass spectrometry-based label-free proteomics to explore the potential targets of BBR in CRC cells. Comprehensive proteomic profiles demonstrated that of 8051 identified proteins, 503 and 277 differentially expressed proteins (DEPs) were screened out of CACO2 and LOVO cells, respectively. 83 DEPs were overlapped and most of these were down-regulated. A pathway enrichment analysis pinpointed mitochondrial translation, respiratory electron transport and the citric acid (TCA) cycle as biological effectors. The data of proteomics was subsequently confirmed by citrate synthase (CS), Tu translation elongation factor (TUFM), pentatricopeptide repeat domain 3 (PTCD3) and mitochondrial ribosomal protein L48 (MRPL 48) protein measurement. CS protein expression in CRC cells and tissues was higher than it was in normal specimens. Additionally, forcible downregulation of CS led to remarkable cell proliferation inhibition. Taken together, we concluded that the anticancer effects of BBR are attributable to mitochondrial protein synthesis, TCA and respiratory electron transport inhibition and that CS might be a useful therapeutic target in CRC treatment.
Insights
Berberine (BBR) shows promise for colorectal cancer (CRC) treatment by inhibiting mitochondrial functions like protein synthesis and energy production. Citrate synthase (CS) emerges as a potential therapeutic target for CRC.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Berberine (BBR) is a natural compound with potential anticancer properties against colorectal cancer (CRC).
- The precise molecular mechanisms underlying BBR's effects on CRC remain largely unelucidated.
Purpose of the Study:
- To investigate the molecular targets of BBR in colorectal cancer (CRC) cells using proteomics.
- To identify key pathways and proteins affected by BBR treatment in CRC.
Main Methods:
- Mass spectrometry-based label-free proteomics was employed to analyze protein expression changes in BBR-treated CRC cells (CACO2 and LOVO).
- Differentially expressed proteins (DEPs) were identified and subjected to pathway enrichment analysis.
- Key protein expressions were validated using Western blotting, and the functional role of citrate synthase (CS) was assessed.
Main Results:
- Proteomic analysis identified significant numbers of DEPs in both cell lines, with 83 overlapping proteins, predominantly downregulated.
- Enriched pathways included mitochondrial translation, respiratory electron transport, and the citric acid (TCA) cycle.
- Citrate synthase (CS) expression was elevated in CRC tissues and cells; its downregulation significantly inhibited cell proliferation.
Conclusions:
- Berberine exerts anticancer effects in CRC by inhibiting mitochondrial protein synthesis, the TCA cycle, and respiratory electron transport.
- Citrate synthase (CS) is identified as a potential therapeutic target for colorectal cancer treatment.
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