Anticancer effects of Plantago major extract on colorectal and gastric cancer cell lines: an in vitro study and molecular docking analysis.

Objectives: Colorectal cancer and gastric cancer are one of the most prevalent types of cancer and are leading causes of cancer-related mortality worldwide. The chemotherapy is insufficient due to the poor targeting and affinity of drugs, low therapeutic effectiveness, and significant side effects. Consequently, developing effective therapeutic formulations is crucial for treating 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.

Methods: This study aims to evaluate the antiproliferative activity of P. major leaf extract on NIH/3T3 fibroblast cells, AGS gastric, and Caco-2 colorectal cancer cell lines for 24 h using XTT cell viability assay. The apoptotic activity of P. major was examined by detecting caspase 3/7 level in cells. The ROS levels in cells were measured using the DCFH-DA dye. Additionally, it assesses the interaction and binding affinities of the active compounds of P. major with the overexpressed EPCAM through molecular docking.

Results: 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 the 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, such as apigenin, aucubin, baicalein, caffeic acid, and luteolin, towards the EpCAM protein overexpressed in gastric and colorectal cancer.

Conclusions: In conclusion, the P. major can be a promising effective therapeutic strategy for gastrointestinal cancers.