ABCG2 downregulation in glioma stem cells enhances the therapeutic efficacy of demethoxycurcumin.

Abstract

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.

• Authors: Long Chen, Lei Shi, Wenhua Wang, Youxin Zhou
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 26 Pg. 43237-43247 (Jun 27 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28591733 (Publication Type: Journal Article)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• Antineoplastic Agents
• Diarylheptanoids
• Neoplasm Proteins
• Reactive Oxygen Species
• Curcumin
• demethoxycurcumin

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2 (metabolism)
• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation
• Curcumin (analogs & derivatives, pharmacology)
• Diarylheptanoids
• Down-Regulation
• Drug Resistance, Neoplasm
• Glioblastoma (drug therapy, metabolism, pathology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Proteins (metabolism)
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Random Allocation
• Reactive Oxygen Species (metabolism)
• Transfection
• Xenograft Model Antitumor Assays