Vitexin, an HIF-1alpha inhibitor, has anti-metastatic potential in PC12 cells.
Vitexin, a natural flavonoid compound identified as apigenin-8-C-b-D-glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory properties. In this study, we investigated its effect on hypoxia-inducible factor-1a (HIF-1a) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells. Vitexin inhibited HIF-1a in PC12 cells, but not in HOS or HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A, enolase 1, and collagen type III in the PC12 cells. We found that vitexin inhibited the migration of PC12 cells as well as their invasion rates, and it also inhibited tube formation by human umbilical vein endothelium cells (HUVECs). Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N-terminal kinase (JNK), but not of extracellular-signal regulated protein kinase (ERK), implying that it acts in part via the JNK pathway. Overall, these results suggest the potential use of vitexin as a treatment for diseases such as cancer.
Choi
Hwa Jung
HJ
Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeonju 561-756, Korea.
Eun
Jae Soon
JS
Kim
Bang Geul
BG
Kim
Sun Yeou
SY
Jeon
Hoon
H
Soh
Yunjo
Y
D000818:Animals; D047310:Apigenin / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D047310:Apigenin; C032731:vitexin