Cyclooxygenase-2 inhibitor prevents radiation-enhanced infiltration of F98 glioma cells in brain of Fischer rat

Desmarais, Guillaume; Charest, Gabriel; Fortin, David; Bujold, Rachel; Mathieu, David; Paquette, Benoît

doi:10.3109/09553002.2015.1043756

Cited by 25 publications

(16 citation statements)

References 35 publications

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“…The microenvironment of glioblastoma tumors is characterized by the infiltration of hyperactivated immune cells, which aggravate disease progression. Thus, it can be hypothesized that inhibition of lipid metabolism can also reduce inflammation at tumor sites [88][89][90]. However, the potential side effects of pyrrolidine-2 deter its use in vivo.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Zhang

Cui

Amiri

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tIncreased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme.

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Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Zhang

Cui

Amiri

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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“…Petersen et al found that inhibitors of PTGS2 could act as radiosensitizing agents and reduce the proliferation rate of tumor cell lines. While Inoue et al claimed that PTGS2 inhibitors enhanced the effects of radiotherapy on prostate cancer and largely prevented the stimulation of F98 cell infiltration into the brain, Yang et al found that celecoxib, a PTGS2 ‐selective inhibitor, sensitized the responsiveness of these medulloblastoma cells to IR exposure in vitro. PTGS2 ‐induced radioresistance was negatively regulated through the phosphorylation of p38 at Tyr182 and that the phosphorylation of p38 induced by TNF‐alpha reduced the expression of Bcl‐2, BCL‐XL, but increased β‐catenin and E‐cadherin, leading to the decreased invasiveness of cells .…”

Section: Discussionmentioning

confidence: 99%

Activation of PTGS2/NF‐κB signaling pathway enhances radiation resistance of glioma

Tan

Liu

et al. 2019

Cancer Medicine

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Objective We focused on the effects of PTGS2/NF‐κB signaling pathway on the radiation resistance of glioma in the study. Methods We downloaded the microarray data from the Gene Expression Omnibus (GEO) database. We verified transfection successfully through QRT‐PCR analysis. Immunofluorescence was used to detect γH2AX content under 2 Gy radiation. The survival rates of cells under 2 Gy irradiation were tested by clonogenic survival assay. Flow cytometry was used to detect cell cycle. Western blot was applied to detect the expression of NF‐κB pathway‐related proteins. We also used MTT assay to detect the proliferation of cells. Results In this research, we discovered that the expression of the PTGS2 was upregulated in radiation‐resistant glioma cells. The radio‐tolerance rate of U87 cells was obviously elevated after the overexpression of PTGS2. The radioresistance of U87R cells was significantly reduced after the knockdown of PTGS2. After radiotherapy, the number of cells arrested in G2/M phase decreased after PTGS2 overexpression in U87cells but increased in PTGS2 knockdown in U87R cells. The survival rate of U87 and U87R cells under radiation decreased significantly after the addition of NF‐κB inhibitor. The proliferation of U87 cells was suppressed by radiation and the addition of Bay 11. In addition, PTGS2 activated NF‐κB signaling pathway and prevented DNA damage after radiotherapy. Lastly, PTGS2 was proved to facilitate tumor cell proliferation and improve the radio‐tolerance. Conclusion PTGS2/NF‐κB signaling pathway was involved in radio‐tolerance of glioma cells, which provided a new insight into glioma therapy.

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“…Increasing evidence suggests that an inflammatory, immunosuppressive tumor microenvironment may promote invasion by GBM cells [54, 55] through the activation of pathways that recruit myeloid precursors. One interesting possible mechanism involved in the sensitivity of GBM tumors to vosaroxin and vosaroxin plus RT is the recruitment of myeloid cells such as monocytes, macrophages, and microglia.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

et al. 2017

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PurposeGlioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT).ResultsVosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10−100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow–derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model.Materials and MethodsCellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferase-transfected U251 cells by bioluminescence and magnetic resonance imaging.ConclusionsVosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6-methylguanine methyltransferase-negative and -positive cell lines.

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Cyclooxygenase-2 inhibitor prevents radiation-enhanced infiltration of F98 glioma cells in brain of Fischer rat

Abstract: Our results indicate the importance of reducing the inflammatory response of normal brain tissue following irradiation in an effort to extend median survival in F98 tumor-bearing rats.

Cited by 25 publications

References 35 publications

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Activation of PTGS2/NF‐κB signaling pathway enhances radiation resistance of glioma

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

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