Plaunotol inhibits gastric cancer cells by induction of apoptosis

5903 BACKGROUND AND AIM: Plaunotol, a kind of isoprenoid, is an anti-gastric ulcer agent, available for clinical use since more than 20 years ago in Japan and Thailand. Some kinds of isoprenoids, such as docetaxel, paclitaxel, or geranylgeraniol, have been reported to have strong anti-cancer activities, but the effect of Plaunotol on cancer has not been evaluated. Here, we aimed to investigate the anti-tumor effect of Plaunotol on gastric cancer. METHODS: The gastric adenocarcinoma cell lines, namely MKN-45, and AZ-521, were used. Plaunotol was kindly gifted by Sankyo Co. Ltd., and tested at various concentrations (10, 20, 30 and 40 μmol/L). The proliferative activity of gastric cancer cells was assessed by the MTS assay. The annexin V / PI staining, and the TUNEL assay were used to analyze the induction of apoptosis. In addition, to clarify the mechanisms of the apoptosis induction, the activation of caspases-8, -9 and -3 was evaluated by flow-cytometry. RESULTS: Plaunotol treatment for 24h dose-dependently inhibited the proliferative activity of both gastric cancer cell lines tested. This inhibitory effect was dependent on induction of apoptosis, as confirmed by the annexin V / PI staining and the TUNEL assay. Both the caspase-8 and caspase-9 cascades were activated in the apoptosis induced by Plaunotol. CONCLUSION: Plaunotol dose-dependently inhibited the proliferative activity of gastric cancer cell lines, by induction of cell apoptosis. It should be a promising anti-gastric cancer agent, and since it is already available for clinical use in Japan and Thailand, and, in contrast to docetaxel and paclitaxel, which have strong side-effects, is proved to have little adverse effects, clinical trials should be started to confirm its properties in human beings.