Dihydrocapsaicin Secreted by RYK Silenced Bone Marrow-Derived Mesenchymal Stem Cells Triggers Apoptosis of Gastric Cancer Cells

Introduction: Bone marrow-derived mesenchymal stem cells (BMSCs) are recruited into the gastric cancer (GC) microenvironment and promote progression, though the underlying mechanisms remain unclear. This study investigated how RYK-silenced BMSCs induce GC cell apoptosis, with a focus on the novel role of dihydrocapsaicin (DHC). Methods: BMSCs were transfected with RYK siRNA or negative controls and co-cultured with NCI-N87 cells to investigate their interactions. Cancer cell cycle and apoptosis were assessed by flow cytometry, while protein levels of Caspase3, Bax, and Bcl-2 in NCI-N87 cells were determined via Western blot. Metabolomics analyzed differential metabolites in BMSCs. Additionally, NCI-N87 cells were treated with DHC, and their proliferation, apoptosis, and apoptosis-related protein expression were evaluated after different DHC treatments. Results: Compared to NCI-N87 cells cultured alone, co-culture with si-NC-modified BMSCs reduced apoptosis in NCI-N87 cells. However, co-culture with si-RYK-BMSCs significantly increased apoptosis. Additionally, DHC, a metabolic product secreted by BMSCs after RYK interference, suppresses NCI-N87 cell growth, promotes cell death, and increases the expression of apoptosis-related proteins. Conclusion: RYK-silenced BMSCs induce NCI-N87 apoptosis, likely through increased DHC secretion, highlighting DHC as a novel mediator in GC progression. Keywords: dihydrocapsaicin, RYK, bone marrow-derived mesenchymal stem cells, gastric cancer, apoptosis