Recent evidences have suggested that genistein, a beneficial isoflavonoid, exerts marked anti-proliferative action on colorectal cancer (CRC) cells. However, the exact molecular mechanisms behind anti-CRC effect of genistein have not been elucidated. In current report, a systemic pharmacology analysis was used to disclose the anti-CRC mechanism of genistein prior to performing experimentative certification. As shown in network pharmacology findings, a total of 189 common targets and 9 hard-core targets of genistein-anti-CRC were collected and identified. And the detailed anti-CRC functions and pathways mediated by genistein were uncovered. In further certification, human CRC samples resulted in elevated protein and mRNA expressions of myeloid leukemia cell differentiation protein (MCL1), beta amyloid A4 protein (APP), and vascular endothelial growth factor receptor 2 (KDR). In animal experiment, genistein-treated tumor-transplanted nude mice exhibited reduced tumor growth, accompanied with dose-dependent down-regulations of MCL1, APP, and KDR proteins and mRNAs. Taken together, the integrated bioinformatic and experimental findings uncover the anti-CRC mechanisms and targets mediated by genistein. Significantly, parts of hard-core biotargets were experimentally verified before clinical application, including MCL1, APP, and KDR.
Keywords: colorectal cancer; genistein; mechanisms; network pharmacology; targets.
© 2020 International Union of Biochemistry and Molecular Biology.