INTRODUCTION: Gastric cancer (GC), widely known as stomach cancer, is a critical health concern across the world. Natural products have been renowned for millennia and are highly reputable as a fashionable supply of therapeutic agents. Erucin is a naturally occuring isothiocyanate found in various cruciferous vegetables, particularly in rocket (arugula) and certain types of broccoli. This study aimed to evaluate the anti-cancer effect and mechanistic role of erucin on GC cell lines.
METHODS: To understand the pharmacological potential of erucin, we employed network pharmacology, molecular docking, molecular dynamics simulations, and in-vitro studies. These methods contributed to a holistic understanding of the mechanisms, interactions, and efficacy of erucin in GC.
RESULTS: Network pharmacology analysis revealed 10 key targets including SRC, AKT1, mTOR1, BCL2, and HIF1A in the gastric cancer pathway. Molecular docking showed that erucin exhibited higher binding affinities for SRC, AKT1, and mTOR1 among these targets, with stable interactions validated by dynamics simulation for SRC and AKT1. Erucin induced concentration and time-dependent cytotoxicity in AGS cells with a 24 h IC₅₀ of 77.3 ± 6.6 µM and 48 h IC₅₀ of 52.6 ± 1.12 µM. Acridine orange/ethidium bromide (AO/EtBr) dual staining assay showed a dose-dependent increase in apoptotic cells, characterized by nuclear condensation and membrane blebbing. Erucin treatment markedly inhibited the colony formation ability of AGS cell line in a dose-dependent manner. AGS cells treated with Erucin exhibited significantly reduced migration rates compared to control cells. Western blotting showed Bax upregulation, Bcl-2 downregulation, and cytochrome c release with downregulated SRC. These findings have antiproliferative and anti-cancer effects on AGS cells.
CONCLUSION: Erucin exhibits potent anti-cancer activity in AGS gastric cancer cells by directly targeting critical oncogenic regulators including SRC, mTORC1, and AKT1. Its multi-targeted interaction profile and ability to inhibit cell proliferation, migration, and colony formation strongly support its therapeutic potential in gastric cancer management.
