Geraniol induces apoptosis in gastric cancer cells by inhibiting the Wnt/β-catenin pathway.

[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.