Chamomile extract as a potential regulator of mitochondrial apoptosis and the Wnt/β-catenin pathway in AGS and KATO III cells

Abstract Gastric cancer comprises molecularly heterogeneous subtypes with distinct therapeutic responses. Although Matricaria chamomilla L. (chamomile) possesses anti-inflammatory and antioxidant properties, its molecular effects in different gastric cancer subtypes remain poorly understood. This study investigated the antiproliferative and apoptosis-inducing effects of aqueous chamomile extract in AGS (p53 wild-type) and KATO III (p53-mutant) gastric cancer cells. HPLC-DAD-ESI-MS/MS characterized the extract. Cell viability was assessed by MTT assay, apoptosis by DAPI and Annexin V/PI, mitochondrial membrane potential by JC-1 staining, and gene/protein expression by qRT-PCR and ELISA. Subcellular fractionation evaluated β-catenin nuclear translocation. The extract contained 22.41 mg GAE/g phenolics and 161.9 mg QE/g flavonoids, with 14 identified compounds. Chamomile extract induced apoptosis, increased BAX and Caspase-3 , decreased Bcl-2 and CTNNB1 , and reduced downstream targets AXIN2 , CCND1 , and MYC . Subcellular fractionation revealed decreased nuclear β-catenin (60% in AGS; 52% in KATO III) and increased cytosolic β-catenin, reducing the nuclear-to-cytoplasmic ratio (83% in AGS; 75% in KATO III). Changes were consistently more pronounced in AGS cells. These findings indicate that aqueous chamomile extract promotes mitochondrial apoptosis and modulates Wnt/β-catenin signaling in gastric cancer cells, with differential responses between AGS and KATO III cells highlighting the influence of molecular heterogeneity.