Cinnamomi Ramulus Inhibits the Growth of Colon Cancer Cells Via Akt/ERK Signaling Pathways

Background: Colon cancer (CC) has the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancers has recently received increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism of against CC still needs to be fully evaluated. Methods TCMSP and China National Knowledge Infrastructure database were obtained to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. Then, we evaluated the therapeutic effect of CR on CC by oral administration in CC-bearing mice and performed in vitro cellular functional verifications. Next, the potential CC-related targets were further identified by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis results were validated by a series of cellular functional and molecular biological assays. Results In this study, we first found that CR has potential therapeutic effects on cancers. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, and it could inhibit the viability and motility of CC cells. Meanwhile, we further obtained 111 potential core therapeutic targets, and enrichment analyses showed that CR could induce the apoptosis and cell cycle arrest in CC cells by blocking the Akt/ERK signaling pathways. The above virtual results were further verified. Next, we used ultraperformance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) to identify 5 key components from the crude extract of CR. Molecular docking analysis revealed that taxifolin is mostly likely to be a potential key active ingredient. Conclusions In summary, our results indicate that CR has good prospects in the treatment of CC.