PMID- 23934681
OWN - NLM
STAT- MEDLINE
DCOM- 20140212
LR  - 20171116
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 134
IP  - 5
DP  - 2014 Mar 1
TI  - Oroxylin A has therapeutic potential in acute myelogenous leukemia by dual 
      effects targeting PPARgamma and RXRalpha.
PG  - 1195-206
LID - 10.1002/ijc.28435 [doi]
AB  - Oroxylin A (OA) is a flavonoid derived from a Chinese herb that has previously 
      been reported to inhibit the proliferation of several cancer cell lines. It is 
      found that OA significantly inhibited the growth of myeloid leukemia cell lines 
      and as xenografts in immunodeficient mice and primary blasts from acute 
      myelogenous leukemia (AML) patients. Furthermore, OA-induced cell cycle arrest 
      and differentiation were observed in OA-treated AML cell lines. OA-induced 
      increase of CD11b/CD14 expression was reversed by GW9662, a specific PPARgamma 
      inhibitor, or transient transfection with PPARgamma siRNA. Docking study showed OA 
      bound to ligand-binding domain of PPARgamma via forming hydrogen bonds with Arg288 
      and Leu340 sites. Results of fluorescence polarization-based ligand assay 
      verified PPARgamma-binding activity of OA, and in OA-treated cells, intranuclear 
      accumulation and increased binding activity of PPARgamma to PPRE were detected. We 
      also found that GW9662 attenuated OA-induced upregulation of C/EBPbeta, an important 
      regulator of leukemic differentiation, and p21, which is a potent inhibitor of 
      CDKs that can inhibit phosphorylation of Rb by cyclin D1-CDK4 complexes. 
      Moreover, our results showed that OA displayed synergistic effects with all-trans 
      retinoic acid and VD3 in part related to reduction of intranuclear phosphorylated 
      RXRalpha that has been reported to block nuclear receptor/RXRalpha heterodimer 
      transcriptional activity. This reduction of phosphorylated RXRalpha was associated 
      with inhibition of the specific upstream MAP kinase ERK1/2. We suggest that OA 
      may provide a novel complement to AML treatment by its dual effects of augmenting 
      PPARgamma activity and sensitizing nuclear receptors to specific ligands.
CI  - (c) 2013 UICC.
FAU - Hui, Hui
AU  - Hui H
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 
      People's Republic of China.
FAU - Chen, Yan
AU  - Chen Y
FAU - Yang, Hao
AU  - Yang H
FAU - Zhao, Kai
AU  - Zhao K
FAU - Wang, Qian
AU  - Wang Q
FAU - Zhao, Li
AU  - Zhao L
FAU - Wang, Xiaotang
AU  - Wang X
FAU - Li, Zhiyu
AU  - Li Z
FAU - Lu, Na
AU  - Lu N
FAU - Guo, Qinglong
AU  - Guo Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130903
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (2-chloro-5-nitrobenzanilide)
RN  - 0 (Anilides)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Flavonoids)
RN  - 0 (PPAR gamma)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
SB  - IM
EIN - Int J Cancer. 2020 Feb 15;146(4):E25. PMID: 31849054
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Anilides/pharmacology
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/genetics
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Flavonoids/*pharmacology/therapeutic use
MH  - G1 Phase/drug effects
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*drug therapy/pathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - PPAR gamma/*drug effects/metabolism
MH  - Retinoid X Receptor alpha/*drug effects/metabolism
OTO - NOTNLM
OT  - AML
OT  - PPARgamma
OT  - RXRalpha
OT  - differentiation
OT  - oroxylin A
EDAT- 2013/08/13 06:00
MHDA- 2014/02/13 06:00
CRDT- 2013/08/13 06:00
PHST- 2013/03/04 00:00 [received]
PHST- 2013/07/29 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/02/13 06:00 [medline]
AID - 10.1002/ijc.28435 [doi]
PST - ppublish
SO  - Int J Cancer. 2014 Mar 1;134(5):1195-206. doi: 10.1002/ijc.28435. Epub 2013 Sep 
      3.