Abstract

Glioblastoma multiforme (GBM) is the most aggressive type characterized by relapse and resistance even with the combination of radio- and chemotherapy. The presence of glioma stem cells (GSCs) has been shown to contribute to tumorigenesis, recurrence and treatment resistance. Particularly, CD133-positive glioma cells have been shown to represent the subpopulation that confers glioma radioresistance and suggested to be the source of tumor recurrence after radiation. Thus, a better understanding and the development of agents which target GSCs could potentially lead to a significant improvement in treating GBM patients. Here, we demonstrated that GRP78 (an antistress protein) was highly expressed in GBM cells along with β-catenin and Notch and correlated to the development of GSCs. CD133+ GSCs exhibited enhanced migration/invasion and self-renewal abilities. When GRP78 was silenced, GSC properties were suppressed and the sensitivity towards irradiation increased. In addition, the level of microRNA 205 appeared to be negatively associated with GRP78 expression. Our previous study indicated that pterostilbene (PT) possessed anticancer stem cell properties in hepatocellular carcinoma. Thus, we examined whether PT is also effective against GSCs. We found that PT-treated GSCs exhibited suppressed self-renewal and irradiation-resistant abilities. PT-mediated effects were associated with an increase of miR-205. Finally, we showed that PT treatment suppressed tumorigenesis in GSC xenograft mice. In conclusion, we provided evidence that GRP78/miR-205 axis played an important role in GSC maintenance and irradiation resistance. PT treatment suppressed GSC development via negatively modulating GRP78 signaling. PT may be considered for combined therapeutic agent to enhance irradiation efficacy in GBM patients.

Original languageEnglish
Pages (from-to)466-475
Number of pages10
JournalJournal of Nutritional Biochemistry
Volume26
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Stem cells
Glioma
Stem Cells
Irradiation
Glioblastoma
Recurrence
pterostilbene
Carcinogenesis
Catenins
Chemotherapy
Radiotherapy
MicroRNAs
Heterografts
Therapeutics
Combination Drug Therapy
Tumors
Hepatocellular Carcinoma
Maintenance
Radiation

Keywords

  • CD133+ glioma stem cells
  • Glucose-regulated protein, 78 kDa (GRP78)
  • Irradiation resistance
  • miR-205
  • Pterostilbene

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Pterostilbene suppressed irradiation-resistant glioma stem cells by modulating GRP78/miR-205 axis. / Huynh, Thanh Tuan; Lin, Chien Min; Lee, Wei Hwa; Wu, Alexander T H; Lin, Yen Kuang; Lin, Yuh Feng; Yeh, Chi-Tai; Wang, Liang Shun.

In: Journal of Nutritional Biochemistry, Vol. 26, No. 5, 01.05.2015, p. 466-475.

Research output: Contribution to journalArticle

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abstract = "Glioblastoma multiforme (GBM) is the most aggressive type characterized by relapse and resistance even with the combination of radio- and chemotherapy. The presence of glioma stem cells (GSCs) has been shown to contribute to tumorigenesis, recurrence and treatment resistance. Particularly, CD133-positive glioma cells have been shown to represent the subpopulation that confers glioma radioresistance and suggested to be the source of tumor recurrence after radiation. Thus, a better understanding and the development of agents which target GSCs could potentially lead to a significant improvement in treating GBM patients. Here, we demonstrated that GRP78 (an antistress protein) was highly expressed in GBM cells along with β-catenin and Notch and correlated to the development of GSCs. CD133+ GSCs exhibited enhanced migration/invasion and self-renewal abilities. When GRP78 was silenced, GSC properties were suppressed and the sensitivity towards irradiation increased. In addition, the level of microRNA 205 appeared to be negatively associated with GRP78 expression. Our previous study indicated that pterostilbene (PT) possessed anticancer stem cell properties in hepatocellular carcinoma. Thus, we examined whether PT is also effective against GSCs. We found that PT-treated GSCs exhibited suppressed self-renewal and irradiation-resistant abilities. PT-mediated effects were associated with an increase of miR-205. Finally, we showed that PT treatment suppressed tumorigenesis in GSC xenograft mice. In conclusion, we provided evidence that GRP78/miR-205 axis played an important role in GSC maintenance and irradiation resistance. PT treatment suppressed GSC development via negatively modulating GRP78 signaling. PT may be considered for combined therapeutic agent to enhance irradiation efficacy in GBM patients.",
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author = "Huynh, {Thanh Tuan} and Lin, {Chien Min} and Lee, {Wei Hwa} and Wu, {Alexander T H} and Lin, {Yen Kuang} and Lin, {Yuh Feng} and Chi-Tai Yeh and Wang, {Liang Shun}",
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T1 - Pterostilbene suppressed irradiation-resistant glioma stem cells by modulating GRP78/miR-205 axis

AU - Huynh, Thanh Tuan

AU - Lin, Chien Min

AU - Lee, Wei Hwa

AU - Wu, Alexander T H

AU - Lin, Yen Kuang

AU - Lin, Yuh Feng

AU - Yeh, Chi-Tai

AU - Wang, Liang Shun

PY - 2015/5/1

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AB - Glioblastoma multiforme (GBM) is the most aggressive type characterized by relapse and resistance even with the combination of radio- and chemotherapy. The presence of glioma stem cells (GSCs) has been shown to contribute to tumorigenesis, recurrence and treatment resistance. Particularly, CD133-positive glioma cells have been shown to represent the subpopulation that confers glioma radioresistance and suggested to be the source of tumor recurrence after radiation. Thus, a better understanding and the development of agents which target GSCs could potentially lead to a significant improvement in treating GBM patients. Here, we demonstrated that GRP78 (an antistress protein) was highly expressed in GBM cells along with β-catenin and Notch and correlated to the development of GSCs. CD133+ GSCs exhibited enhanced migration/invasion and self-renewal abilities. When GRP78 was silenced, GSC properties were suppressed and the sensitivity towards irradiation increased. In addition, the level of microRNA 205 appeared to be negatively associated with GRP78 expression. Our previous study indicated that pterostilbene (PT) possessed anticancer stem cell properties in hepatocellular carcinoma. Thus, we examined whether PT is also effective against GSCs. We found that PT-treated GSCs exhibited suppressed self-renewal and irradiation-resistant abilities. PT-mediated effects were associated with an increase of miR-205. Finally, we showed that PT treatment suppressed tumorigenesis in GSC xenograft mice. In conclusion, we provided evidence that GRP78/miR-205 axis played an important role in GSC maintenance and irradiation resistance. PT treatment suppressed GSC development via negatively modulating GRP78 signaling. PT may be considered for combined therapeutic agent to enhance irradiation efficacy in GBM patients.

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