Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis

Yi Ping Yang, Yuh Lih Chang, Pin I. Huang, Guang Yuh Chiou, Ling Ming Tseng, Shih Hwa Chiou, Ming Hsiung Chen, Ming Teh Chen, Yang Hsin Shih, Chin Hong Chang, Chuan Chih Hsu, Hsin I. Ma, Chin Tien Wang, Lo-Lin Tsai, Cheng Chia Yu, Charn Jung Chang

研究成果: 雜誌貢獻文章

79 引文 (Scopus)

摘要

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133 + TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133 + in vitro and in vivo. Furthermore, treatment of GBM-CD133 + with 100μM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133 + and facilitated the differentiation of GBM-CD133 + into GBM-CD133 - or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway.
原文英語
頁(從 - 到)976-993
頁數18
期刊Journal of Cellular Physiology
227
發行號3
DOIs
出版狀態已發佈 - 三月 2012
對外發佈Yes

指紋

Neoplastic Stem Cells
Radiation Tolerance
Glioblastoma
Tumors
Small Interfering RNA
Radiotherapy
Polyphenols
Microarrays
resveratrol
Brain
Genes
Apoptosis
Radiation
Neoplasms
Astrocytoma
Vitis
Therapeutic Uses
Brain Neoplasms
Proteins
Therapeutics

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

引用此文

Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis. / Yang, Yi Ping; Chang, Yuh Lih; Huang, Pin I.; Chiou, Guang Yuh; Tseng, Ling Ming; Chiou, Shih Hwa; Chen, Ming Hsiung; Chen, Ming Teh; Shih, Yang Hsin; Chang, Chin Hong; Hsu, Chuan Chih; Ma, Hsin I.; Wang, Chin Tien; Tsai, Lo-Lin; Yu, Cheng Chia; Chang, Charn Jung.

於: Journal of Cellular Physiology, 卷 227, 編號 3, 03.2012, p. 976-993.

研究成果: 雜誌貢獻文章

Yang, YP, Chang, YL, Huang, PI, Chiou, GY, Tseng, LM, Chiou, SH, Chen, MH, Chen, MT, Shih, YH, Chang, CH, Hsu, CC, Ma, HI, Wang, CT, Tsai, L-L, Yu, CC & Chang, CJ 2012, 'Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis', Journal of Cellular Physiology, 卷 227, 編號 3, 頁 976-993. https://doi.org/10.1002/jcp.22806
Yang, Yi Ping ; Chang, Yuh Lih ; Huang, Pin I. ; Chiou, Guang Yuh ; Tseng, Ling Ming ; Chiou, Shih Hwa ; Chen, Ming Hsiung ; Chen, Ming Teh ; Shih, Yang Hsin ; Chang, Chin Hong ; Hsu, Chuan Chih ; Ma, Hsin I. ; Wang, Chin Tien ; Tsai, Lo-Lin ; Yu, Cheng Chia ; Chang, Charn Jung. / Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis. 於: Journal of Cellular Physiology. 2012 ; 卷 227, 編號 3. 頁 976-993.
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title = "Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis",
abstract = "Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133 + TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133 + in vitro and in vivo. Furthermore, treatment of GBM-CD133 + with 100μM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133 + and facilitated the differentiation of GBM-CD133 + into GBM-CD133 - or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway.",
author = "Yang, {Yi Ping} and Chang, {Yuh Lih} and Huang, {Pin I.} and Chiou, {Guang Yuh} and Tseng, {Ling Ming} and Chiou, {Shih Hwa} and Chen, {Ming Hsiung} and Chen, {Ming Teh} and Shih, {Yang Hsin} and Chang, {Chin Hong} and Hsu, {Chuan Chih} and Ma, {Hsin I.} and Wang, {Chin Tien} and Lo-Lin Tsai and Yu, {Cheng Chia} and Chang, {Charn Jung}",
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T1 - Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis

AU - Yang, Yi Ping

AU - Chang, Yuh Lih

AU - Huang, Pin I.

AU - Chiou, Guang Yuh

AU - Tseng, Ling Ming

AU - Chiou, Shih Hwa

AU - Chen, Ming Hsiung

AU - Chen, Ming Teh

AU - Shih, Yang Hsin

AU - Chang, Chin Hong

AU - Hsu, Chuan Chih

AU - Ma, Hsin I.

AU - Wang, Chin Tien

AU - Tsai, Lo-Lin

AU - Yu, Cheng Chia

AU - Chang, Charn Jung

PY - 2012/3

Y1 - 2012/3

N2 - Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133 + TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133 + in vitro and in vivo. Furthermore, treatment of GBM-CD133 + with 100μM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133 + and facilitated the differentiation of GBM-CD133 + into GBM-CD133 - or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway.

AB - Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133 + TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133 + in vitro and in vivo. Furthermore, treatment of GBM-CD133 + with 100μM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133 + and facilitated the differentiation of GBM-CD133 + into GBM-CD133 - or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway.

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