PMID- 27085528
OWN - NLM
STAT- MEDLINE
DCOM- 20170217
LR  - 20181113
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Linking)
VI  - 142
IP  - 7
DP  - 2016 Jul
TI  - Oroxylin A, a natural anticancer flavonoid compound, induces differentiation of 
      t(8;21)-positive Kasumi-1 and primary acute myeloid leukemia cells.
PG  - 1449-59
LID - 10.1007/s00432-016-2160-1 [doi]
AB  - PURPOSE: AML1/ETO fusion gene is one of disease-causing genes of t(8;21)-positive 
      acute myeloid leukemia (AML). Oroxylin A (OA) has showed anticancer effects on 
      other cancer cells. Here, studies were conducted to determine the antileukemia 
      effect of OA on t(8;21)-positive AML cells in vitro and in vivo. MATERIALS AND 
      METHODS: The effects of OA on cell viability of t(8;21)-positive Kasumi-1 and 
      primary AML cells were analyzed by MTT assay. Cell differentiation was examined 
      by NBT reduction assay, flow cytometry analysis for CD11b/CD14, and Giemsa stain. 
      Protein expressions were determined by Western blots. Immunofluorescence assay 
      was used to verify the effect of OA on HDAC-1 expression in vivo. 
      Immunohistochemical staining was applied to evaluate leukemic infiltration of 
      AML-bearing NOD/SCID mice. RESULTS: OA enhanced NBT reduction activity and 
      CD11b/CD14 expression of AML1/ETO-positive AML cells markedly. Results of Giemsa 
      staining also demonstrated that OA could induce the morphologic changes with 
      reduction of nuclear/cytoplasmic ratios, suggesting the cell differentiation 
      induced by OA. Further study showed that OA decreased the expression of fusion 
      protein AML1/ETO and down-regulated HDAC-1 protein levels in vitro and in vivo. 
      Moreover, OA increased the expression of differentiation-related proteins C/EBPalpha 
      and P21. Acetylation levels of histones were also advanced obviously after 
      treatment of OA. In vivo study indicated that OA could prolong the survival of 
      AML-bearing NOD/SCID mice and reduce leukocytic infiltration of the spleen. 
      CONCLUSIONS: All these results suggested that OA might be a novel candidate agent 
      for differentiation therapy for AML1/ETO-positive AML and the mechanism required 
      further investigation.
FAU - Hui, Hui
AU  - Hui H
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and 
      Pharmacovigilance, Ministry of Education, JiangSu Key Laboratory of Drug Design 
      and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 
      210009, People's Republic of China.
FAU - Zhang, Xiaoxiao
AU  - Zhang X
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and 
      Pharmacovigilance, Ministry of Education, JiangSu Key Laboratory of Drug Design 
      and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 
      210009, People's Republic of China.
FAU - Li, Hui
AU  - Li H
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and 
      Pharmacovigilance, Ministry of Education, JiangSu Key Laboratory of Drug Design 
      and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 
      210009, People's Republic of China.
FAU - Liu, Xiao
AU  - Liu X
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and 
      Pharmacovigilance, Ministry of Education, JiangSu Key Laboratory of Drug Design 
      and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 
      210009, People's Republic of China.
FAU - Shen, Le
AU  - Shen L
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and 
      Pharmacovigilance, Ministry of Education, JiangSu Key Laboratory of Drug Design 
      and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 
      210009, People's Republic of China.
FAU - Zhu, Yu
AU  - Zhu Y
AD  - Department of Hematology, The First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People's 
      Republic of China.
FAU - Xu, Jingyan
AU  - Xu J
AD  - Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, 210008, People's Republic of China. 
      xjy1967@sina.com.
FAU - Guo, Qinglong
AU  - Guo Q
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and 
      Pharmacovigilance, Ministry of Education, JiangSu Key Laboratory of Drug Design 
      and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 
      210009, People's Republic of China. anticancer_drug@163.com.
FAU - Lu, Na
AU  - Lu N
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and 
      Pharmacovigilance, Ministry of Education, JiangSu Key Laboratory of Drug Design 
      and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 
      210009, People's Republic of China. luna555@163.com.
LA  - eng
PT  - Journal Article
DEP - 20160416
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (Flavonoids)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RUNX1 Translocation Partner 1 Protein)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (RUNX1T1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Differentiation/*drug effects
MH  - *Chromosomes, Human, Pair 12
MH  - *Chromosomes, Human, Pair 8
MH  - Core Binding Factor Alpha 2 Subunit/metabolism
MH  - Flavonoids/*pharmacology
MH  - Histone Deacetylase 1/metabolism
MH  - Humans
MH  - Leukemia, Myeloid, Acute/genetics/*pathology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Proto-Oncogene Proteins/metabolism
MH  - RUNX1 Translocation Partner 1 Protein
MH  - Transcription Factors/metabolism
MH  - *Translocation, Genetic
OTO - NOTNLM
OT  - AML
OT  - AML1/ETO
OT  - Differentiation
OT  - HDAC-1
EDAT- 2016/04/18 06:00
MHDA- 2017/02/18 06:00
CRDT- 2016/04/18 06:00
PHST- 2016/02/28 00:00 [received]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/04/18 06:00 [entrez]
PHST- 2016/04/18 06:00 [pubmed]
PHST- 2017/02/18 06:00 [medline]
AID - 10.1007/s00432-016-2160-1 [pii]
AID - 10.1007/s00432-016-2160-1 [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2016 Jul;142(7):1449-59. doi: 10.1007/s00432-016-2160-1. 
      Epub 2016 Apr 16.