Abstract Objectives This study investigated whether the active ingredients of Pinellia pedatisecta Schott extract (PE) inhibit colorectal cancer (CRC) by targeting the Warburg effect, a common cancer hallmark, and to elucidate the involved mechanism. Methods The active ingredients of PE were identified by high performance liquid chromatography (HPLC). The efficacy of the beta-sitosterol (BS), baicalein, and guanosine (Guo) combination was then evaluated in vivo. In vitro, cell viability, migration, and invasion capabilities were investigated by CCK-8, scratch assay, and Transwell assays, respectively. Network pharmacology was employed to identify potential targets related to the Warburg effect, which were subsequently validated in vitro. Key findings HPLC identified three active ingredients in PE: BS, baicalein, and Guo. The mice exhibited tumor weight loss and volume reduction after BS-baicalein-Guo treatment. In addition, BS-baicalein-Guo elevated apoptosis of HCT-116 cells, while significantly reducing their proliferation in vivo. Besides, BS-baicalein-Guo diminished glucose uptake, lactate and ATP, as well as the expression of glycolysis-related proteins (HK2 and PKM2) and extracellular signal-regulated kinase (ERK) and epidermal growth factor receptor (EGFR) phosphorylation in HCT-116 cells, while NSC228155 (EGFR activator) ameliorated these phenomena. Conclusions The BS-baicalein-Guo combination synergistically alleviates the Warburg effect in CRC by suppressing the EGFR/ERK pathway, highlighting its potential as a therapeutic target.
Zhou et al. (Tue,) studied this question.