TY - JOUR
T1 - Chrysin inhibits expression of hypoxia-inducible factor 1-α through reducing hypoxia-inducible factor-1α stability and inhibiting its protein synthesis
AU - Fu, Beibei
AU - Xue, Jing
AU - Li, Zhaodong
AU - Shi, Xianglin
AU - Jiang, Bing Hua
AU - Fang, Jing
PY - 2007/1
Y1 - 2007/1
N2 - 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-1α (HIF-1α and vascular endothelial growth factor in human prostate cancer DU145 cells. Chrysin inhibited insulin-induced expression of HIF-1α by reducing its stability. Chrysin increases ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation. In addition, chrysin interfered with interaction between HIF-1α and heat shock protein 90. Chrysin was also found to inhibit HIF-1α expression through AKT signaling. Inhibition of HIF-1α 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-1α and provide a new sight into the mechanisms of chrysin against cancer.
AB - 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-1α (HIF-1α and vascular endothelial growth factor in human prostate cancer DU145 cells. Chrysin inhibited insulin-induced expression of HIF-1α by reducing its stability. Chrysin increases ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation. In addition, chrysin interfered with interaction between HIF-1α and heat shock protein 90. Chrysin was also found to inhibit HIF-1α expression through AKT signaling. Inhibition of HIF-1α 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-1α and provide a new sight into the mechanisms of chrysin against cancer.
UR - http://www.scopus.com/inward/record.url?scp=33846842258&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846842258&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-06-0526
DO - 10.1158/1535-7163.MCT-06-0526
M3 - Article
C2 - 17237281
AN - SCOPUS:33846842258
SN - 1535-7163
VL - 6
SP - 220
EP - 226
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
IS - 1
ER -