Chrysin inhibits expression of hypoxia-inducible factor-1alpha through reducing hypoxia-inducible factor-1alpha stability and inhibiting its protein synthesis.
Chrysin is a natural flavonoid and has been shown recently to have anticancer effects. However, the mechanisms that chrysin inhibits cancers are not well known. In this study, we investigated the effects of chrysin on expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor in human prostate cancer DU145 cells. Chrysin inhibited insulin-induced expression of HIF-1alpha by reducing its stability. Chrysin increases ubiquitination and degradation of HIF-1alpha by increasing its prolyl hydroxylation. In addition, chrysin interfered with interaction between HIF-1alpha and heat shock protein 90. Chrysin was also found to inhibit HIF-1alpha expression through AKT signaling. Inhibition of HIF-1alpha by chrysin resulted in abrogation of vascular endothelial growth factor expression. Finally, we showed that chrysin inhibited DU145 xenograft-induced angiogenesis in nude mice. Taken together, these results suggest that chrysin is a potent inhibitor of HIF-1alpha and provide a new sight into the mechanisms of chrysin against cancers.
Fu
Beibei
B
The Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xue
Jing
J
Li
Zhaodong
Z
Shi
Xianglin
X
Jiang
Bing-Hua
BH
Fang
Jing
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D003094:Collagen; D004338:Drug Combinations; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007797:Laminin; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011509:Proteoglycans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013816:Thermodynamics; D015533:Transcriptional Activation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004338:Drug Combinations; D005419:Flavonoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; C043561:chrysin; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt