Investigation of galangin against colorectal cancer through MAPK signaling pathway modulation

Abstract

Colorectal cancer (CRC) is a major global health burden with poor prognosis due to high metastasis and recurrence rates. Galangal has shown potential anti-cancer effects, but its mechanisms remain unclear. This study aims to dig out the anti-CRC effects of galangal and its potential mechanisms. Network pharmacology was used to explore the bioactive compounds and predict potential targets and pathways of galangal against CRC. Additionally, we employed a wide range of assays to identify the impact of the bioactive compound of galangal on the biological function of CRC cells in vitro, including CCK-8, EdU staining, colony formation, wound healing, transwell assay and Western blot analysis. Through network pharmacology analysis, we identified galangin as the bioactive compound of galangal. Galangin significantly inhibited the proliferation and migration of CRC cells in vitro with low toxicity. It arrested cell cycle at the G0/G1 phase and promoted apoptosis by increasing reactive oxygen species (ROS) levels and decreasing mitochondrial membrane potential. RNA sequencing revealed that galangin modulated the MAPK signaling pathway, which was further confirmed by Western blot analysis showing inhibition of MAPK activation. Importantly, MAPK signaling pathway activator was used to further verified that galangin inhibited HCT15 cells proliferation by suppressing MAPK signaling pathway. Our research suggested that galangin, which is the bioactive compound of galangal, demonstrates potent inhibitory effects on CRC cell proliferation and metastasis by modulating the MAPK signaling pathway. Our findings suggest that galangin is a promising candidate for CRC therapeutics, warranting further investigation for in vivo even clinical application.

Keywords: Apoptosis; Cell cycle; Colorectal cancer; Galangin; MAPK signaling pathway; ROS.