Integrative Pharmacoinformatic and Experimental Validation of Indonesian Red Algae as Novel Functional Food for Anti‐Gastric Cancer Agents

ABSTRACT Gastric cancer remains a major global health burden with limited therapeutic options due to resistance and toxicity of current treatments. Marine red algae— Gracilaria edulis , Eucheuma denticulatum , and Kappaphycus striatus —are underexplored sources of bioactive compounds that may offer multi‐targeted, low‐toxicity agents for gastric cancer therapy. This study integrated phytochemical profiling, structure–activity relationship (SAR) analysis, network pharmacology, molecular docking, molecular dynamics simulations, and in vitro validation. SAR and docking analyses showed strong affinities of key compounds, including camptothecin and 24(S),25‐epoxycholesterol, with gastric cancer targets (PTGER3, TGFBR1, IGF1R, CDK6, BRD4). Molecular dynamics confirmed the stability of camptothecin–TGFBR1 interactions. Kappaphycus striatus extract (KSE) significantly downregulated TGF‐β1 expression in MKN‐45 cells in a dose‐dependent manner. Cytotoxicity assays demonstrated that KSE, camptothecin, and 24(S),25‐epoxycholesterol selectively inhibited AGS and MKN‐45 gastric cancer cells while sparing normal epithelial cells. The findings highlight Indonesian red algae as promising, safe, and sustainable sources of multi‐targeted anti‐gastric cancer agents. In particular, KSE and its bioactive constituents exhibit both cytotoxic and epigenetic modulatory effects, underscoring their potential for future therapeutic development.