Valproic Acid Inhibits Angiogenesis In Vitro and Glioma Angiogenesis In Vivo in the Brain

Osuka, Satoru; Takano, Shingo; Watanabe, Shinya; Ishikawa, Eiichi; Yamamoto, Tetsuya; Matsumura, Akira

doi:10.2176/nmc.52.186

Cited by 61 publications

(49 citation statements)

References 30 publications

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“…The inhibiting rate of VPA group, DDP group and VPA+DDP group were as follows: 40.7%, 45.3%, 58% (as in B), they were significantly higher than control group (P<0.01). The cell cycle distribution changed in experimental group, the S-phase was decrease (as in C DOI:http://dx.doi.org/10.7314/APJCP.2012.13.8 Osuka et al, 2012). Based on our in vitro and in vivo data, we found that VEGF and MMP-9 were reduced but the expression of E-cadherin was increased after treated with VPA.…”

Section: Discussionmentioning

confidence: 72%

Effects of Valproic Acid on Proliferation, Apoptosis, Angiogenesis and Metastasis of Ovarian Cancer in Vitro and in Vivo

Song¹,

Rong²,

Geng³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

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Section: Discussionmentioning

confidence: 72%

Effects of Valproic Acid on Proliferation, Apoptosis, Angiogenesis and Metastasis of Ovarian Cancer in Vitro and in Vivo

Song¹,

Rong²,

Geng³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…VPA is also an HDACi (34,35) that has shown potent antitumor effects in vitro and in vivo in a variety of cancers, including GBM (36,37). This drug is a chromatin remodeling agent, consequently able to strongly modify gene expression (38-40), inducing cancer cell differentiation, apoptosis and growth arrest.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic targeting of glioma stem cells: Short-term and long-term treatments with valproic acid modulate DNA methylation and differentiation behavior, but not temozolomide sensitivity

et al. 2016

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Abstract. Glioblastoma (GBM) is the most aggressive tumor of the central nervous system. GBM is a fatal tumor, incurable by conventional therapies. One of the factors underlying tumor recurrence and poor long-term survival is the presence of a cancer stem-like cell population, termed glioma stem cells (GSCs), which is particularly resistant to chemotherapy and radiotherapy and supports tumor self-renewal. The aim of the present study was to evaluate the impact and difference in effects of short-term and long-term treatments with valproic acid (VPA), a histone deacetylase inhibitor, on seven GSC lines. We investigated for the first time the changes in the genome-wide DNA methylation profile and the differentiation behavior of GSCs induced by short-term and long-term VPA treatments. Moreover, we verified VPA sensitivity after long-term VPA pretreatment and, notably, the results provide evidence of a subpopulation more resistant to further VPA treatments. Finally, since short-term VPA treatment induced a reversal of the MGMT methylation status, we aimed to sensitize GSCs to temozolomide, the drug commonly used for this tumor, using this regimen. The overall data highlighted the heterogeneous behavior of GSC lines that is representative of tumor heterogeneity in GBM. The VPA effects were variable among these cell lines in terms of pro-differentiating ability and DNA methylation switch. Here, we attempted to identify a suitable therapy for the eradication of the stem cell subpopulation, which is mandatory to achieve an effective treatment for this tumor. Differentiation-inducing and epigenetic therapies are the most promising approaches to affect the multiple properties of GSCs and, finally, defeat GBM.

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“…Since then, several studies have provided support to the hypothesis that valproic acid derivatives are a promising drug class for the treatment of GBM. Valproic acid attenuated the growth of glioma cells by inhibiting angiogenesis (48) and inducing differentiation (49). In addition, valproic acid increased the sensitivity of glioma cells to conventional GBM therapies, including TMZ and γ-radiation (50,51).…”

Section: Antipsychotics As Anti-gbm Therapeuticsmentioning

confidence: 99%

Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges

2016

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Abstract. Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor, with tragically little therapeutic progress over the last 30 years. Surgery provides a modest benefit, and GBM cells are resistant to radiation and chemotherapy. Despite significant development of the molecularly targeting strategies, the clinical outcome of GBM patients remains dismal. The challenges inherent in developing effective GBM treatments have become increasingly clear, and include resistance to standard treatments, the blood-brain barrier, resistance of GBM stem-like cells, and the genetic complexity and molecular adaptability of GBM. Recent studies have collectively suggested that certain antipsychotics harbor antitumor effects and have potential utilities as anti-GBM therapeutics. In the present review, the anti-tumorigenic effects and putative mechanisms of antipsychotics, and the challenges for the potential use of antipsychotic drugs as anti-GBM therapeutics are reviewed.

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Valproic Acid Inhibits Angiogenesis In Vitro and Glioma Angiogenesis In Vivo in the Brain

Cited by 61 publications

References 30 publications

Effects of Valproic Acid on Proliferation, Apoptosis, Angiogenesis and Metastasis of Ovarian Cancer in Vitro and in Vivo

Effects of Valproic Acid on Proliferation, Apoptosis, Angiogenesis and Metastasis of Ovarian Cancer in Vitro and in Vivo

Epigenetic targeting of glioma stem cells: Short-term and long-term treatments with valproic acid modulate DNA methylation and differentiation behavior, but not temozolomide sensitivity

Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges

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