The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice.

Abstract

The flavonoid nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), found in Citrus depressa Rutaceae, a popular citrus fruit in Okinawa, Japan, reportedly inhibits the production of pro-matrix metalloproteinase (proMMP)-1, 3, and 9 in rabbit synovial fibroblasts in vitro. In the present study, we demonstrated the inhibitory effects of nobiletin on the proliferation of the cancer cell line, TMK- 1, and its production of MMPs. In the SCID mouse model, we found that nobiletin inhibited the formation of peritoneal dissemination nodules from TMK-1. The enzymatic activity of MMP-9 expressed in culture medium obtained from a co-culture of TMK-1 and mouse fibroblastic cells was inhibited by nobiletin in a concentration-dependent manner. In the SCID mouse model, total weight of dissemination nodules was significantly lower in the treated group compared with the vehicle control group (0.07 g vs. 0.78 g, P = 0.0059). The total number of dissemination nodules was also significantly lower than in the vehicle control group (7.5 vs. 69.3 / body, P = 0.0001). These results suggest that nobiletin may be a candidate anti-metastatic drug for prevention of peritoneal dissemination of gastric cancer.

• Authors: A Minagawa, Y Otani, T Kubota, N Wada, T Furukawa, K Kumai, K Kameyama, Y Okada, M Fujii, M Yano, T Sato, A Ito, M Kitajima
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 92 Issue 12 Pg. 1322-8 (Dec 2001) ISSN: 0910-5050 [Print] Japan
• PMID: 11749698 (Publication Type: Journal Article)

Chemical References

• Flavones
• Flavonoids
• nobiletin
• Matrix Metalloproteinases

Topics

• Animals
• Body Weight (drug effects)
• Cell Division (drug effects)
• Citrus (chemistry)
• Dose-Response Relationship, Drug
• Flavones
• Flavonoids (chemistry, pharmacology, therapeutic use)
• Humans
• Matrix Metalloproteinases (metabolism)
• Mice
• Mice, SCID
• Neoplasm Transplantation
• Organ Size (drug effects)
• Organ Specificity
• Peritoneal Neoplasms (drug therapy, pathology, secondary)
• Stomach Neoplasms (drug therapy, enzymology, pathology)
• Tumor Cells, Cultured