Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo

Amit Budhraja; Ning Gao; Zhuo Zhang; Young-Ok Son; Senping Cheng; Xin Wang; Songze Ding; Andrew Hitron; Gang Chen; Jia Luo; Xianglin Shi

doi:10.1158/1535-7163.MCT-11-0343

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Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo

Journal article

Open access

Peer reviewed

Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo

Amit Budhraja, Ning Gao, Zhuo Zhang, Young-Ok Son, Senping Cheng, Xin Wang, Songze Ding, Andrew Hitron, Gang Chen, Jia Luo, …

Molecular cancer therapeutics, Vol.11(1), pp.132-142

01/2012

DOI: 10.1158/1535-7163.MCT-11-0343

PMCID: PMC4430727

PMID: 22084167

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Abstract

In this study, we investigated the functional role of Akt and c-jun-NH(2)-kinase (JNK) signaling cascades in apigenin-induced apoptosis in U937 human leukemia cells and anti-leukemic activity of apigenin in vivo. Apigenin induced apoptosis by inactivation of Akt with a concomitant activation of JNK, Mcl-1 and Bcl-2 downregulation, cytochrome c release from mitochondria, and activation of caspases. Constitutively active myristolated Akt prevented apigenin-induced JNK, caspase activation, and apoptosis. Conversely, LY294002 and a dominant-negative construct of Akt potentiated apigenin-induced apoptosis in leukemia cells. Interruption of the JNK pathway showed marked reduction in apigenin-induced caspase activation and apoptosis in leukemia cells. Furthermore, in vivo administration of apigenin resulted in attenuation of tumor growth in U937 xenografts accompanied by inactivation of Akt and activation of JNK. Attenuation of tumor growth in U937 xenografts by apigenin raises the possibility that apigenin may have clinical implications and can be further tested for incorporating in leukemia treatment regimens.

Signal Transduction

Animals

Apigenin - metabolism

Apigenin - pharmacology

Apoptosis - drug effects

Caspases - metabolism

Cell Line, Tumor

Chromones - pharmacology

Cytochromes c - metabolism

Down-Regulation

Humans

JNK Mitogen-Activated Protein Kinases - metabolism

Jurkat Cells

Leukemia - drug therapy

Leukemia - metabolism

Leukemia - pathology

Mice

Mice, Nude

Mitochondria - metabolism

Morpholines - pharmacology

Myeloid Cell Leukemia Sequence 1 Protein

Proto-Oncogene Proteins c-akt - metabolism

Proto-Oncogene Proteins c-bcl-2 - metabolism

RNA Interference

RNA, Small Interfering

U937 Cells

Xenograft Model Antitumor Assays

Details

Title: Subtitle: Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo
Creators: Amit Budhraja - University of Kentucky
Ning Gao
Zhuo Zhang
Young-Ok Son
Senping Cheng
Xin Wang
Songze Ding
Andrew Hitron
Gang Chen
Jia Luo
Xianglin Shi
Resource Type: Journal article
Publication Details: Molecular cancer therapeutics, Vol.11(1), pp.132-142
DOI: 10.1158/1535-7163.MCT-11-0343
PMID: 22084167
PMCID: PMC4430727
ISSN: 1535-7163
eISSN: 1538-8514
Grant note: R01 AA015407 / NIAAA NIH HHS R01 CA116697 / NCI NIH HHS R01 ES015375 / NIEHS NIH HHS R01 CA119028 / NCI NIH HHS
Language: English
Date published: 01/2012
Academic Unit: Pathology
Record Identifier: 9984201113402771

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