10-HDA Suppresses the Growth of Gastric Cancer Cells Through Inducing Apoptosis and G0/G1 Cell Cycle Arrest

Background/Objectives: Gastric cancer (GC) remains a major global health challenge, highlighting the need for safe and effective bioactive compounds for prevention and treatment. Although 10-hydroxy-2-decenoic acid (10-HDA)—a distinctive bioactive fatty component of royal jelly—has demonstrated anticancer activity in several malignancies, its efficacy and underlying mechanisms in GC remain poorly understood. In the present study, the anticancer activity of 10-HDA was systematically investigated in human GC MKN-45 cells. Methods: MKN-45 cells were treated with 10-HDA across a concentration range of 0.09–1.50 mM. Cell viability, proliferation, and clonogenic growth were evaluated using MTT, scratch wound assay, and colony formation assays. Apoptosis was analyzed by flow cytometry and Western blotting. To explore the underlying molecular mechanisms, transcriptome analysis was conducted, and the results were further validated using flow cytometry, qRT-PCR, and Western blotting. Results: Treatment with 10-HDA significantly inhibited cell viability, proliferation, and clonogenic growth in a dose- and time-dependent manner, with IC50 values of 1.24 ± 0.15 mM, 0.96 ± 0.08 mM, and 0.42 ± 0.06 mM at 24 h, 48 h, and 72 h, respectively. Flow cytometric analysis revealed that apoptosis was markedly induced, with the apoptotic rate increasing from 21.3% in control cells to 78.1% following treatment with 1.50 mM 10-HDA. This was accompanied by upregulation of BAX, downregulation of Bcl-2, and increased activation of caspase-3. Transcriptomic profiling identified significant alterations in DNA replication- and cell cycle-related pathways. Consistently, experimental validation demonstrated that 10-HDA induced pronounced G0/G1-phase cell cycle arrest; downregulation of CDK2 and cyclin D1; reduced retinoblastoma protein phosphorylation; and upregulation of the cyclin-dependent kinase inhibitor CDKN1A. Conclusions: These findings demonstrate that 10-HDA suppresses the malignant phenotype of gastric cancer cells by coordinated activation of apoptosis and cell cycle blockade. Although further in vivo studies and pharmacological experiments are required to evaluate its bioavailability and therapeutic potential, this study provides preliminary mechanistic insights into the effects of 10-HDA on gastric cancer cells.