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

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.