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Valproic acid promotes radiosensitization in meningioma stem-like cells.

Chiou HY, Lai WK, Huang LC, Huang SM, Chueh SH, Ma HI, Hueng DY - Oncotarget (2015)

Bottom Line: Anchorage-independent growth (AIG) was reduced by VPA.AIG was further reduced by combined treatment with irradiation.Oct4 was further decreased by combined treatment with irradiation.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

Expression of Oct4 in meningioma sphere cells (MgSCs) and meningioma adherent cells (MgACs)(A) Representative bright field micrographs showed growth of cultured MgSCs and MgACs in stem cell culture medium or DMEM with 10% FBS, respectively. (B) Oct4 expressions in MgSCs and MgACs were examined by immuno-fluorescence staining with anti-Oct4 antibody. Magnification, 100x. PI staining indicated the nucleus (red). Merged PI and Oct4 are shown in yellow. Bars: 100 μm. (C) Oct4 mRNA expression was examined by RT-PCR, with GAPDH as an internal control. Data are representative of 3 independent experiments.
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Figure 1: Expression of Oct4 in meningioma sphere cells (MgSCs) and meningioma adherent cells (MgACs)(A) Representative bright field micrographs showed growth of cultured MgSCs and MgACs in stem cell culture medium or DMEM with 10% FBS, respectively. (B) Oct4 expressions in MgSCs and MgACs were examined by immuno-fluorescence staining with anti-Oct4 antibody. Magnification, 100x. PI staining indicated the nucleus (red). Merged PI and Oct4 are shown in yellow. Bars: 100 μm. (C) Oct4 mRNA expression was examined by RT-PCR, with GAPDH as an internal control. Data are representative of 3 independent experiments.

Mentions: To further characterize the stem-like properties of MgSCs, the expression of stem cell marker was analyzed by immunofluorescence and RT-PCR. Of the induced pluripotent stem (iPS) cell factors, Oct4 was first examined since it could reprogram adult stem cells to iPS cells as a single factor [18]. Day 2 cultured MgSCs formed spheres (Figure 1A) and were positive for Oct4 (Figure 1B), but daughter MgACs had relatively low expression on Oct4. Oct4 mRNA expressions in MgSCs and MgACs were determined by RT-PCR (Figure 1C).


Valproic acid promotes radiosensitization in meningioma stem-like cells.

Chiou HY, Lai WK, Huang LC, Huang SM, Chueh SH, Ma HI, Hueng DY - Oncotarget (2015)

Expression of Oct4 in meningioma sphere cells (MgSCs) and meningioma adherent cells (MgACs)(A) Representative bright field micrographs showed growth of cultured MgSCs and MgACs in stem cell culture medium or DMEM with 10% FBS, respectively. (B) Oct4 expressions in MgSCs and MgACs were examined by immuno-fluorescence staining with anti-Oct4 antibody. Magnification, 100x. PI staining indicated the nucleus (red). Merged PI and Oct4 are shown in yellow. Bars: 100 μm. (C) Oct4 mRNA expression was examined by RT-PCR, with GAPDH as an internal control. Data are representative of 3 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496410&req=5

Figure 1: Expression of Oct4 in meningioma sphere cells (MgSCs) and meningioma adherent cells (MgACs)(A) Representative bright field micrographs showed growth of cultured MgSCs and MgACs in stem cell culture medium or DMEM with 10% FBS, respectively. (B) Oct4 expressions in MgSCs and MgACs were examined by immuno-fluorescence staining with anti-Oct4 antibody. Magnification, 100x. PI staining indicated the nucleus (red). Merged PI and Oct4 are shown in yellow. Bars: 100 μm. (C) Oct4 mRNA expression was examined by RT-PCR, with GAPDH as an internal control. Data are representative of 3 independent experiments.
Mentions: To further characterize the stem-like properties of MgSCs, the expression of stem cell marker was analyzed by immunofluorescence and RT-PCR. Of the induced pluripotent stem (iPS) cell factors, Oct4 was first examined since it could reprogram adult stem cells to iPS cells as a single factor [18]. Day 2 cultured MgSCs formed spheres (Figure 1A) and were positive for Oct4 (Figure 1B), but daughter MgACs had relatively low expression on Oct4. Oct4 mRNA expressions in MgSCs and MgACs were determined by RT-PCR (Figure 1C).

Bottom Line: Anchorage-independent growth (AIG) was reduced by VPA.AIG was further reduced by combined treatment with irradiation.Oct4 was further decreased by combined treatment with irradiation.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus