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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

Effects of VPA and irradiation on colony formation of MgSCsMgSCs were treated with or without 2 mM VPA for 24 h, followed by irradiation 5 Gy. 24 h after irradiation, MgSCs were transferred and cultured in soft agar for 16 days. The colony formations were determined by soft agar assay and the quantitative results are shown. Bars, mean±SEM; *p < 0.05, **p < 0.01, and #p < 0.001 showed significant differences. Data are representative of 3 independent experiments.
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Figure 4: Effects of VPA and irradiation on colony formation of MgSCsMgSCs were treated with or without 2 mM VPA for 24 h, followed by irradiation 5 Gy. 24 h after irradiation, MgSCs were transferred and cultured in soft agar for 16 days. The colony formations were determined by soft agar assay and the quantitative results are shown. Bars, mean±SEM; *p < 0.05, **p < 0.01, and #p < 0.001 showed significant differences. Data are representative of 3 independent experiments.

Mentions: Since VPA could induce cell differentiation and anchorage-independent growth (AIG) was a key criterion for tumor metastasis [17], the effects of VPA and irradiation on MgSCs AIG were determined by soft-agar assay. The number of colony formations in MgSCs treated with radiation or VPA alone was significantly reduced (*p < 0.05 and #p < 0.001, respectively) (Figure 4). Moreover, combined treatment significantly reduced colony formation compared to both the untreated control (#p < 0.001) and irradiation alone (**p < 0.01).


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)

Effects of VPA and irradiation on colony formation of MgSCsMgSCs were treated with or without 2 mM VPA for 24 h, followed by irradiation 5 Gy. 24 h after irradiation, MgSCs were transferred and cultured in soft agar for 16 days. The colony formations were determined by soft agar assay and the quantitative results are shown. Bars, mean±SEM; *p < 0.05, **p < 0.01, and #p < 0.001 showed significant differences. 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 4: Effects of VPA and irradiation on colony formation of MgSCsMgSCs were treated with or without 2 mM VPA for 24 h, followed by irradiation 5 Gy. 24 h after irradiation, MgSCs were transferred and cultured in soft agar for 16 days. The colony formations were determined by soft agar assay and the quantitative results are shown. Bars, mean±SEM; *p < 0.05, **p < 0.01, and #p < 0.001 showed significant differences. Data are representative of 3 independent experiments.
Mentions: Since VPA could induce cell differentiation and anchorage-independent growth (AIG) was a key criterion for tumor metastasis [17], the effects of VPA and irradiation on MgSCs AIG were determined by soft-agar assay. The number of colony formations in MgSCs treated with radiation or VPA alone was significantly reduced (*p < 0.05 and #p < 0.001, respectively) (Figure 4). Moreover, combined treatment significantly reduced colony formation compared to both the untreated control (#p < 0.001) and irradiation alone (**p < 0.01).

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