Quercetin promotes glioma growth in a rat model.

We have previously demonstrated that quercetin (Quer), a polyphenol widely found in vegetables, decreased glioma cell growth in vitro. Here, we asked whether this compound could affect glioma growth in an in vivo rat glioma model. We found that daily intraperitoneal Quer (50 mg/kg) injections lead to a concentration of 0.

Resveratrol abrogates the temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the temozolomide-induced senescence in glioma cells.

Background: Temozolomide (TMZ) is the most widely used drug to treat glioblastoma (GBM), which is the most common and aggressive primary tumor of the Central Nervous System and one of the hardest challenges in oncotherapy. TMZ is an alkylating agent that induces autophagy, apoptosis and senescence in GBM cells. However, therapy with TMZ increases survival after diagnosis only from 12 to 14.

Autophagy interplay with apoptosis and cell cycle regulation in the growth inhibiting effect of resveratrol in glioma cells.

Prognosis of patients with glioblastoma (GBM) remains very poor, thus making the development of new drugs urgent. Resveratrol (Rsv) is a natural compound that has several beneficial effects such as neuroprotection and cytotoxicity for several GBM cell lines. Here we evaluated the mechanism of action of Rsv on human GBM cell lines, focusing on the role of autophagy and its crosstalk with apoptosis and cell cycle control.

Protective profile of oxcarbazepine against oxygen-glucose deprivation in organotypic hippocampal slice culture could involve PI3K cell signaling pathway.

Objective: Brain ischemia results in cellular degeneration and loss of brain function. Oxcarbazepine (OXC), one of the newer antiepileptic drugs, has been demonstrating its efficacy on wide spectrum neurological disorders. In this paper, we investigated the neuroprotective profile of OXC in an in vitro model of ischemia, which consists in the exposure of organotypic hippocampal slice cultures to oxygen and glucose deprivation.

Resveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cells.

Glioma is the most frequent and malignant primary human brain tumor with dismal prognosis despite multimodal therapy. Resveratrol and quercetin, two structurally related and naturally occurring polyphenols, are proposed to have anticancer effects. We report here that resveratrol and quercetin decreased the cell number in four glioma cell lines but not in rat astrocytes.

Homocysteine increases neuronal damage in hippocampal slices receiving oxygen and glucose deprivation.

Homocystinuria is an inherited metabolic disorder caused by severe deficiency of cystationine beta-synthase activity, resulting in the tissue accumulation of homocysteine (Hcy). Affected patients usually present many signs and symptoms such as seizures, mental retardation, atherosclerosis and stroke. The aim of this study is to evaluate in vivo and in vitro effects of Hcy using hippocampal slices from Wistar rats exposed to oxygen and glucose deprivation (OGD), followed by reoxygenation, an in vitro model of hypoxic-ischemic events.

Beta-amyloid peptide toxicity in organotypic hippocampal slice culture involves Akt/PKB, GSK-3beta, and PTEN.

In the present study we investigated the toxicity induced by exposing organotypic slice culture to beta-amyloid peptide 25-35 (25microM) for 1, 3, 6, 12, 24 and 48h. To elucidate a mechanism involved in its toxicity, we studied the PI3-K cell signaling pathway, particularly Akt/PKB, GSK-3beta, and PTEN proteins. Cell death was quantified by propidium iodide uptake and proteins were analyzed by immunoblotting.

Antiproliferative effect of quercetin in the human U138MG glioma cell line.

Recent epidemiological and dietary intervention studies in animals and humans have suggested that diet-derived flavonoids, in particular quercetin, may play a beneficial role by preventing or inhibiting tumorigenesis. The aim of this study was to evaluate whether quercetin may act differently on cancer and normal neuronal tissue. In order to investigate this, the U138MG human glioma cell line and hippocampal organotypic cultures were used.

Protective effect of resveratrol against oxygen-glucose deprivation in organotypic hippocampal slice cultures: Involvement of PI3-K pathway.

Here we investigated the neuroprotective effect of resveratrol in an in vitro model of ischemia. We used organotypic hippocampal cultures exposed to oxygen-glucose deprivation (OGD). In OGD-vehicle exposed cultures, about 46% of the hippocampus was labeled with PI, indicating a robust percentage of cell death.

The effects of estradiol on estrogen receptor and glutamate transporter expression in organotypic hippocampal cultures exposed to oxygen--glucose deprivation.

The molecular basis of estrogen-mediated neuroprotection against brain ischemia remains unclear. In the present study, we investigated changes in expression of estrogen receptors (ERs) alpha and beta and excitatory amino acid transporters (EAAT) 1 and 2 in rat organotypic hippocampal slice cultures treated with estradiol and subsequently exposed to oxygen--glucose deprivation (OGD). Pretreatment with 17beta-estradiol (10 nM) for 7 days protected the CA1 area of hippocampus against OGD (60 min), reducing cellular injury by 46% compared to the vehicle control group.

Hyperhomocysteinemia increases damage on brain slices exposed to in vitro model of oxygen and glucose deprivation: prevention by folic acid.

In the present study we evaluate the effects of homocysteine on cellular damage using hippocampal slices from Wistar rats exposed to oxygen and glucose deprivation (OGD, followed by reoxygenation), an in vitro model of hypoxic-ischemic events. For chronic treatment, we induced elevated levels of homocysteine in blood (500 microM), comparable to those of human homocystinuria, and in brain (60 nmol/g wet tissue) of young rats by subcutaneous injections of homocysteine (0.3-0.

Neuroprotection and protein damage prevention by estradiol replacement in rat hippocampal slices exposed to oxygen-glucose deprivation.

Here we investigated the effects of estradiol replacement in ovariectomized female rats using hippocampal slices exposed to oxygen-glucose deprivation (OGD). OGD induced lactate dehydrogenase (LDH) release to the incubation medium, what was assumed as a parameter of cellular death. In the estradiol-treated group the LDH release was markedly decreased by 23% as compared to the vehicle-treated group.

Estradiol protects against oxygen and glucose deprivation in rat hippocampal organotypic cultures and activates Akt and inactivates GSK-3beta.

Here we investigated the neuroprotective effect of 17beta-estradiol in an in vitro model of ischemia. We used organotypic hippocampal slice cultures, acute or chronically treated with 17beta-estradiol (10 nM), and exposed to oxygen and glucose deprivation (OGD). Cellular death was quantified by measuring uptake of propidium iodide (PI), a marker of dead cells.