Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: Antiproliferative effects, induction of apoptosis and cell cycle deregulation

Aim: To demonstrate the antitumour effects of nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone), a citrus flavonoid extracted from Citrus depressa Hayata, on human gastric cancer cell lines TMK-1, MKN-45, MKN-74 and KATO-III. Materials and methods: 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, the TdT-mediated dUTP biotin nick-end labelling (TUNEL) method and cell-cycle analysis revealed that nobiletin acted on these cells in several ways, namely by direct cytotoxicity, induction of apoptosis and modulation of cell cycle. The efficacy of combined treatment of nobiletin with a conventional anticancer drug, CDDP, was also examined. Treatment with nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control. Conclusions: Although the effective dose and administration route of nobiletin require further investigation, our study represents a potential successful linking of this compound with the treatment of gastric cancer.