Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of this study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels of phosphorylated Akt, mTOR, p70S6K and MAPK in the presence of EGF. Furthermore, our results revealed the ability of luteolin to induce caspase and PARP cleavages in glioblastoma cells in addition to promoting cell cycle arrest. Our results demonstrated that luteolin has an inhibitory effect on downstream signalling molecules activated by EGFR, particularly the Akt and MAPK signalling pathways, and provided a rationale for further clinical investigation into the use of luteolin as a therapeutic molecule in the management of glioblastoma.

Objectives Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM. Methods Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses. Key findings Our results showed that apigenin reduced cell viability and proliferation in a dose-and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL. Conclusion Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM.

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Introduction Dosing recommendations for paliperidone long-acting injectable antipsychotic (LAIA) do not include oral antipsychotic (OAP) overlap; however, OAPs are often given concurrently despite limited evidence describing both the risks and benefits of this practice. Methods A retrospective chart review was conducted in patients initiated on paliperidone palmitate (PP) during a psychiatric hospitalization to compare patients who received OAP overlap versus those who did not. The primary outcome is the proportion of patients who receive prescription claims for benztropine, a medication commonly prescribed for extrapyramidal symptoms, at the time of LAIA discontinuation and 6 months postdischarge. Secondary outcomes include prescription claims for beta blockers and diphenhydramine, number of psychiatric emergency visits and hospitalizations, length of stay of the index hospitalization, frequency of LAIA discontinuation and the time to LAIA discontinuation. Results There is a significant difference in the proportion of benztropine prescription claims in the OAP overlap group versus the no-overlap group at the time of LAIA discontinuation (30% vs 0%, P = .046) but not at 6 months postdischarge. There are also significant differences in the number of psychiatric emergency visits (0.7 vs 0.1, P = .02) and psychiatric hospitalizations (0.6 vs 0.1, P = .029) at the time of LAIA discontinuation. No other differences are observed in defined secondary outcomes. Discussion Patients who receive OAP overlap while receiving PP receive more benztropine and have more psychiatric emergency visits and hospitalizations than those treated without OAP. Larger studies with better control for confounding variables are needed to confirm these results.

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