文章基本信息

标题：Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer
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作者：Shi-Hai Yan ; Li-Mu Hu ; Xue-Hui Hao 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：8
页码：1-25
DOI：10.1016/j.isci.2022.104773
语种：English
出版社：Elsevier
摘要：SummaryColorectal cancer is one of the most serious tumors and berberine can inhibit the recurrence and transformation of colorectal adenoma into colorectal cancer. However, the direct binding target proteins of berberine in inhibiting colorectal cancer remain unclear. In this study, the chemical proteomics method was used and demonstrated that berberine is directly bound to pyruvate kinase isozyme type M2 (PKM2) in colorectal cancer cells. The triangular N-O-O triangular structure of berberine contributed to hydrophobic interaction with I119 amino acid residues and π-π interaction with F244 amino acid residues of PKM2 protein. Moreover, berberine was shown to inhibit the reprogramming of glucose metabolism and the phosphorylation of STAT3, down regulate the expression of Bcl-2 and Cyclin D1 genes, ultimately inhibiting the progression of colorectal cancer. This study uncovered the direct binding target protein and mechanism of berberine to improve metabolic reprogramming in colorectal cancer, which is helpful to guide the optimization of berberine.Graphical abstractDisplay OmittedHighlights•Berberine directly targets PKM2 to inhibit colorectal cancer•Berberine forms hydrophobic interaction with I119 and π-π interaction with F244 of PKM2•P-aminobenzoic acid-berberine ester was synthesized to improve the biological activityBiochemistry; Biomolecules; Molecular biology