PMID- 22170854
OWN - NLM
STAT- MEDLINE
DCOM- 20121204
LR  - 20211203
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 26
IP  - 8
DP  - 2012 Aug
TI  - Liquiritigenin inhibits serum-induced HIF-1alpha and VEGF expression via the 
      AKT/mTOR-p70S6K signalling pathway in HeLa cells.
PG  - 1133-41
LID - 10.1002/ptr.3696 [doi]
AB  - Liquiritigenin (LQ) is a non-toxic dietary flavonoid with chemopreventive and 
      anticancer properties. However, the mechanism of its antiangiogenesis remains 
      unclear. Hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream target, vascular 
      endothelial growth factor (VEGF), play a critical role in tumour angiogenesis and 
      represent an attractive chemotherapeutic target. In this study, we investigated 
      the effect of LQ on the molecular mechanism of angiogenesis. We found that LQ 
      inhibited VEGF expression at both mRNA and protein levels. Liquiritigenin did not 
      affect HIF-1alpha expression at the mRNA level, but it dramatically inhibited both 
      serum- and mimicked hypoxic-induced HIF-1alpha protein accumulation in HeLa cells. 
      Furthermore, we showed that LQ inhibited serum-induced expression of HIF-1alpha by 
      reducing its stability and decreased the synthesis in a dose-dependent manner. 
      Mechanistically, we demonstrated that LQ inhibited HIF-1alpha and VEGF expression 
      involved in blocking the protein kinase B (PKB/Akt) signalling pathway, and the 
      mechanisms correlated with dephosphorylation of the mammalian target of rapamycin 
      (mTOR) and its effector ribosomal protein S6 kinase (p70S6K). In addition, LQ 
      inhibited VEGF-induced formation of capillary-like structures in human umbilical 
      vein endothelial cells (HUVEC). Taken together, our study provided valuable 
      insights into the mechanism of antiangiogenic effect of LQ.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Xie, Si-Rou
AU  - Xie SR
AD  - Department of Nutrition and Food Hygiene, Nanjing Medical University, 140 
      Hanzhong Road, Nanjing, Jiangsu 210029, P. R. China.
FAU - Wang, Yu
AU  - Wang Y
FAU - Liu, Chang-Wei
AU  - Liu CW
FAU - Luo, Kang
AU  - Luo K
FAU - Cai, Yun-Qing
AU  - Cai YQ
LA  - eng
PT  - Journal Article
DEP - 20111214
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Flavanones)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - T194LKP9W6 (liquiritigenin)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Flavanones/*pharmacology
MH  - HeLa Cells
MH  - Human Umbilical Vein Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Neovascularization, Pathologic/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis/drug effects
MH  - Protein Stability
MH  - RNA, Messenger/genetics/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism
MH  - Serum/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Transcriptional Activation
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
EDAT- 2011/12/16 06:00
MHDA- 2012/12/10 06:00
CRDT- 2011/12/16 06:00
PHST- 2011/03/10 00:00 [received]
PHST- 2011/09/14 00:00 [revised]
PHST- 2011/09/29 00:00 [accepted]
PHST- 2011/12/16 06:00 [entrez]
PHST- 2011/12/16 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - 10.1002/ptr.3696 [doi]
PST - ppublish
SO  - Phytother Res. 2012 Aug;26(8):1133-41. doi: 10.1002/ptr.3696. Epub 2011 Dec 14.