ABCG2 downregulation in glioma stem cells enhances the therapeutic efficacy of demethoxycurcumin
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Long Chen1,2,*, Lei Shi3,*, Wenhua Wang2,* and Youxin Zhou1
1Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China
2Department of Neurosurgery, Traditional Chinese Medicine Hospital of Kunshan, Affiliated Nanjing University of Traditional Chinese Medicine, Suzhou 215300, P. R. China
3Department of Neurosurgery, The First People’s Hospital of Kunshan Affiliated with Jiangsu University, Suzhou 215300, P. R. China
*These authors have contributed equally to this work
Lei Shi, email: firstname.lastname@example.org
Youxin Zhou, email: email@example.com
Keywords: glioma stem cells, demethoxycurcumin, reactive oxygen species, caspase-3, ABCG2
Received: February 20, 2017 Accepted: April 06, 2017 Published: May 19, 2017
We analyzed the role of ABCG2, a drug transporter, in determining the sensitivity of glioma stem cells (GSCs) to demethoxycurcumin (DMC). We first demonstrated that ABCG2 is more highly expressed in GSCs than primary astrocytes. Modulation of ABCG2 levels in GSCs by transfection of ABCG2 shRNA or a lentiviral vector encoding ABCG2 revealed an inverse relation between ABCG2 levels and DMC-induced GSC growth inhibition. Suppressing ABCG2 increased DMC-induced apoptosis and G0/G1 cell cycle arrest in GSCs. It also increased levels reactive oxygen species (ROS) in GSCs treated with DMC, resulting in increased cytochrome C and caspase-3 activity. When GSCs transfected with ABCG2 shRNA or overexpressing ABCG2 were xenografted and the tumor-bearing, immunodeficient mice were treated with DMC, ABCG2 expression suppressed the tumor proliferation rate (T/C %). These findings demonstrate that ABCG2 expression is critical for DMC resistance in GSCs and is a potential therapeutic target for GBM.
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