Abstract Significance Geraniol (GI), an acyclic monoterpene alcohol, exhibits diverse anti-cancer activities. However, its potential effects against gastric cancer remain poorly understood. Aims The present study aimed to explore whether GI promotes apoptosis in gastric cancer cells, and decipher the possible mechanism underlying this effect. Methods The cell viability and cell cycle distribution of SGC-7901 cells and MKN45 cells were evaluated using MTT assay, MB assay, and flow cytometry. The expression of Bax, Bcl-2, and glycogen synthase kinase-3 (GSK-3β) proteins, the mitochondrial membrane potential (MMP), and cell apoptosis in SGC-7901 cells were determined using Western blotting, JC-1 staining, immunofluorescence analysis, and Annexin V/propidium iodide double staining. In addition, cell apoptosis and the expression of proliferating cell nuclear antigen, Cleaved-caspase-3, Bax, Bcl-2, and GSK-3β proteins in the xenografts were determined using terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling, immunohistochemistry, and Western blotting. Key findings GI significantly inhibited the viability of gastric cancer cells and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. GI also promoted apoptosis and decreased the MMP in gastric cancer cells. Moreover, GI significantly upregulated the Bax/Bcl-2 ratio and downregulated the expression of pGSK-3β and β-catenin both in vitro and in vivo, while increasing the expression of Cleaved-caspase-3 in SGC-7901 cell xenografts. Furthermore, GI reversed the anti-apoptotic effect of the GSK-3β inhibitor—LiCl, confirming its pro-apoptotic role. Conclusion GI suppresses gastric cancer progression both in vitro and in vivo, by inducing apoptosis through inhibition of the Wnt/β-catenin pathway.
Yu et al. (Thu,) studied this question.