Oncotarget

Research Papers:

Valproic acid promotes radiosensitization in meningioma stem-like cells

Hsin-Ying Clair Chiou, Wen-Kuo Lai, Li-Chun Huang, Shih-Ming Huang, Sheau-Huei Chueh, Hsin-I Ma and Dueng-Yuan Hueng _

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Oncotarget. 2015; 6:9959-9969. https://doi.org/10.18632/oncotarget.3692

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Abstract

Hsin-Ying Clair Chiou1, Wen-Kuo Lai2, Li-Chun Huang2, Shih-Ming Huang2, Sheau-Huei Chueh2, Hsin-I Ma1 and Dueng-Yuan Hueng1,2

1 Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.

2 Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.

Correspondence to:

Dueng-Yuan Hueng, email:

Keywords: meningioma, tumor stem-like cells, radiosensitization, valproic acid, Oct4

Received: January 05, 2015 Accepted: March 05, 2015 Published: March 29, 2015

Abstract

Although meningioma stem-like cells have been isolated and characterized, their therapeutic targeting remains a challenge. Meningioma sphere cells (MgSCs) with cancer stem cells properties show chemo- and radioresistance in comparison with meningioma adherent cells (MgACs). We tested the effect of valproic acid (VPA), a commonly used anti-epileptic drug, which passes the blood brain barrier, on cultured MgSCs. VPA reduced the viability of MgSCs and MgACs. In MgSCs, treatment with VPA increased radio-sensitivity, expression of p-cdc2, p-H2AX and cleaved caspase-3 and PARP. Anchorage-independent growth (AIG) was reduced by VPA. AIG was further reduced by combined treatment with irradiation. Expression of a stem cell marker, Oct4, was reduced by VPA. Oct4 was further decreased by combined treatment with irradiation. These results suggest that VPA may be a potential treatment for meningioma through targeting meningioma stem-like cells.


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