The anti-tumor activity and critical active compounds of polyphenols from Chinese dwarf cherry (Cerasus humilis)

BACKGROUND: Cerasus humilis (Bge.) Sok. fruit ( C. humilis) is rich in polyphenols and has a potential anti-tumor effect. However, its anti-tumor functional compositions and mechanism remain unclear. OBJECTIVE: This study aims to investigate the antitumor activity and chemical composition of polyphenols from C. humilis, and to identify the critical antitumor substances and potential mechanisms. METHODS: Polyphenols of 14 germplasms were extracted and purified; the inhibitory effects of C. humilis polyphenols on the proliferation of liver cancer HepG2 cells, colon cancer HCT116 cells, and gastric cancer BGC823 cells were evaluated by MTT assay; polyphenol compounds were identified by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry; partial least squares were utilized to build chemometrics models for selecting anti-tumor compounds; the key targets and pathways of antitumor effects of C. humilis were predicted by network pharmacology. RESULTS: The total polyphenol content ranged from 275.9 to 598.2 mg/100 g fresh weight, with an average of 381.2 mg/100 g FW; C. humilis polyphenols has potent inhibitory effects on liver, colon, and gastric cancer cells; twenty-three polyphenols were identified; a total of 12, 17, and 18 components were anti-liver cancer, anti-colon cancer, and anti-gastric cancer active polyphenols, respectively; TP53, MAPK3, MAPK1, RELA, AKT1, PIK3R1 and other 16 genes are the key anti-tumor targets; pathway in cancer, lipid and atherosclerosis, colorectal cancer, microRNAs in caner, HIF-1 signaling pathway and other pathways are the key pathways for anti-tumor effects of C. humilis. CONCLUSIONS: C. humilis polyphenols can be developed as a functional natural product to intervene in liver, stomach, and colon cancers.