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


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.
Yoshimizu
N
N
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Otani
Y
Y
Saikawa
Y
Y
Kubota
T
T
Yoshida
M
M
Furukawa
T
T
Kumai
K
K
Kameyama
K
K
Fujii
M
M
Yano
M
M
Sato
T
T
Ito
A
A
Kitajima
M
M
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D047309:Flavones / Q000627:therapeutic use*; D006801:Humans; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D047309:Flavones; C008661:nobiletin; D002945:Cisplatin