Resveratrol inhibits hypoxia-induced metastasis potential enhancement by restricting hypoxia-induced factor-1 alpha expression in colon carcinoma cells.
Resveratrol has been shown recently to exhibit antimetastatic effect on various human solid tumors. However, the possible molecular mechanism for its antimetastatic action needs to be elucidated. In this study, we investigated the effect of resveratrol on metastasis potential of colon carcinoma cells under normoxia and hypoxia in vitro. These results showed that, resveratrol can restrict the migration, adhesion, invasion and MMP-9 and MMP-2 secretion in Lovo cells cultured under normoxia and hypoxia. Hypoxia and iron chelator 2,2'-dipyridyl treatment can stimulate the invasion and migration enhancement of Lovo cells, while resveratrol exhibited substantial resistance on the metastasis potential stimulation by inhibiting the mRNA expression of VEGF and MMP-9 in colon carcinoma cells under normoxia and hypoxia, reducing HIF-1 alpha protein expression under hypoxia. Also, iron chelator 2,2'-dipyridyl treatment showed approximately the same effect on metastasis potential as Lovo cells cultured under hypoxia. These data demonstrated that, the antimetastatic effect of resveratrol under hypoxia were associated with the restriction of HIF-1 alpha protein expression and stabilization, which could be a promising drug target for resveratrol in the development of an effective chemopreventive and anticancer therapy in human tumors.
Wu
Hongzhong
H
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Liang
Xin
X
Fang
Yishi
Y
Qin
Xiaoran
X
Zhang
Yuanxing
Y
Liu
Jianwen
J
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol