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Child's Nervous System
Published in: Child's Nervous System 3/2012

01-03-2012 | Original Paper

Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells

Authors: Charn-Jung Chang, Chih-Hung Chiang, Wen-Shin Song, Shen-Kou Tsai, Lin-Chung Woung, Chin-Hong Chang, Shaw-Yeu Jeng, Ching-Yao Tsai, Chuan-Chih Hsu, Hung-Fu Lee, Chi-Shuan Huang, Ming-Chi Yung, Jorn-Hon Liu, Kai-Hsi Lu

Published in: Child's Nervous System | Issue 3/2012

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Abstract

Introduction

CD133 (PROM1) is a potential marker for cancer stem cells (CSCs), including those found in brain tumors. Recently, medulloblastoma (MB)-derived CD133-positive cells were found to have CSC-like properties and were proposed to be important contributors to tumorigenicity, cancer progression, and chemoradioresistance. However, the biomolecular pathways and therapeutic targets specific to MB-derived CSCs remain unresolved.

Materials and methods

In the present study, we isolated CD133+ cells from MB cell lines and determined that they showed increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared to CD133− cells. Bioinformatics analysis suggested that the STAT3 pathway might be important in MB and CD133+ cells. To evaluate the effects of inhibiting the STAT3 pathway, MB-derived CD133+/− cells were treated with the potent STAT3 inhibitor, cucurbitacin I. Treatment with cucurbitacin I significantly suppressed the CSC-like properties and stemness gene signature of MB-derived CD133+ cells. Furthermore, cucurbitacin I treatment increased the apoptotic sensitivity of MB-derived CD133+ cells to radiation and chemotherapeutic drugs. Notably, cucurbitacin I demonstrated synergistic effects with ionizing radiation to inhibit tumorigenicity in MB-CD133+-inoculated mice.

Results

These results indicate that the STAT3 pathway plays a key role in mediating CSC properties in MB-derived CD133+ cells. Targeting STAT3 with cucurbitacin I may therefore represent a novel therapeutic approach for treating malignant brain tumors.
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Metadata
Title
Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells
Authors
Charn-Jung Chang
Chih-Hung Chiang
Wen-Shin Song
Shen-Kou Tsai
Lin-Chung Woung
Chin-Hong Chang
Shaw-Yeu Jeng
Ching-Yao Tsai
Chuan-Chih Hsu
Hung-Fu Lee
Chi-Shuan Huang
Ming-Chi Yung
Jorn-Hon Liu
Kai-Hsi Lu
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
Child's Nervous System / Issue 3/2012
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-011-1672-x

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