Abstract
Colorectal cancer and gastric cancer are one of the most prevalent types of cancer and are leading causes of cancer-related mortality worldwide. The efficacy of chemotherapy is insufficient due to the poor targeting and affinity of drugs, low therapeutic effectiveness, significant side effects, and emergence of drug resistance. Consequently, the development of effective therapeutic formulations is a crucial research area for the treatment of colorectal and gastric cancers. Plantago major (P. major) is a medicinal plant that has been investigated for medical research for cancer therapy owing to its rich phytochemical composition, including aucubin, luteolin, baicalein, apigenin, and caffeic acid derivatives. This study aims to evaluate the antiproliferative activity of P. major herbal extract on NIH/3T3 fibroblast cells, AGS gastric, and Caco-2 colorectal cancer cell lines for 24 hours using XTT cell viability assay. Additionally, it assesses the interaction and binding affinities of the active compounds of P. major with the overexpressed EPCAM through molecular docking. The results demonstrate a dose-dependent anticancer effect of P. major on AGS and Caco-2 cell lines by reducing cell proliferation, increasing intracellular ROS accumulation and activating caspase 3/7 apoptosis pathway. P. major exhibited no significant cytotoxic effects on non-cancerous NIH/3T3 fibroblast cells. Molecular docking analysis confirmed the high binding affinity of active compounds in P. major extract, such as apigenin, aucubin, baicalein, caffeic acid, and luteolin, towards the EpCAM protein overexpressed in gastric and colorectal cancer. In conclusion, the P. major extract can be a promising effective therapeutic strategy for gastrointestinal cancers.