Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer
Shi-Hai Yan,
Li-Mu Hu,
Xue-Hui Hao,
Jiang Liu,
Xi-Ying Tan,
Zhi-Rong Geng,
Jing Ma,
Zhi-Lin Wang
Affiliations
Shi-Hai Yan
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210023, P.R. China; Department of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, P. R. China
Li-Mu Hu
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210023, P.R. China
Xue-Hui Hao
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210023, P.R. China
Jiang Liu
Department of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, P. R. China
Xi-Ying Tan
Department of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, P. R. China
Zhi-Rong Geng
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210023, P.R. China; Corresponding author
Jing Ma
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210023, P.R. China; Corresponding author
Zhi-Lin Wang
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210023, P.R. China; Corresponding author
Summary: Colorectal 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.
