Narirutin Induces Cytotoxicity and Apoptosis in Gastric Cancer Cells Through Oxidative Stress Modulation

Background Gastric cancer remains a major global health challenge, with approximately 1.1 million new cases and 770,000 deaths reported annually. Despite ongoing advancements in therapeutics, the prognosis for patients with advanced gastric cancer remains poor, underscoring the need for novel, safe, and effective treatment options. Natural flavonoids have gained increasing attention due to their multi-targeted mechanisms and low-toxicity profiles. Narirutin, a citrus-derived flavonoid glycoside, has been recognized for its anti-oxidant and anti-inflammatory activities; however, its direct anti-cancer potential in gastric cancer models remains underexplored. Purpose This study aims to investigate the anti-proliferative and apoptosis-inducing effects of narirutin in human gastric adenocarcinoma (AGS) cells, while also assessing its impact on oxidative stress and relevant molecular targets involved in apoptosis and inflammation. Materials and Methods AGS gastric cancer cells were treated with varying concentrations of narirutin. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed via acridine orange/ethidium bromide (AO/EB) staining, while intracellular reactive oxygen species (ROS) levels were measured using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In silico molecular docking studies were conducted to predict narirutin’s binding affinity toward key apoptotic (caspase-3 (CASP3), BCL2-associated X (BAX)) and inflammatory (nuclear factor kappa B subunit 1 (NF-κB1), nuclear factor kappa B subunit 2 (NF-κB2)) proteins, as well as glycolytic enzymes lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB). Results Narirutin treatment led to a concentration-dependent reduction in AGS cell viability, with accompanying morphological features of apoptosis and elevated ROS levels. These findings suggest that narirutin may induce cancer cell death via a pro-oxidant mechanism. Docking studies supported these observations, revealing strong binding affinities with LDHA (−9.4 kcal/mol, 1.524 Å root mean square deviation (RMSD)) and LDHB (−8.7 kcal/mol, 2.449 Å RMSD), along with favorable interactions with CASP3, BAX, NF-κB1, and NF-κB2, indicating its potential to modulate key regulators of apoptosis and inflammation. Conclusion Nursing care is important in terms of educating patients about new treatments, providing support to patients participating in clinical trials, and providing counseling. The findings demonstrate that narirutin exerts pro-apoptotic and pro-oxidant effects on AGS gastric cancer cells, likely by interfering with redox homeostasis and inflammatory signaling pathways. These results provide a mechanistic rationale for further investigation of narirutin as an anti-cancer candidate for gastric cancer.