Glioblastoma (GBM) is a fatal astrocytic glioma with poor prognosis and treatment resistance. Repurposing potential FDA-approved drugs like anti-psychotics can address the concerns in a timely and cost-effective manner. Epidemiological studies have shown that patients with schizophrenic using anti-psychotics have a low incidence of GBM. Therefore, we aimed to investigate the therapeutic potential of atypical anti-psychotic Iloperidone (ILO) alone and in combination with Temozolomide (TMZ) against GBM. The study assessed the growth inhibitory effect of ILO, TMZ, and their combination (ILO + TMZ) on U-87MG and T-98G cell lines using an MTT assay. The drug interaction coefficient (CDI) was determined, and doses with synergistic effects were used for subsequent experiments, including migratory, invasion, and TUNEL assays. The expressions of DRD2, β-catenin, Dvl2, Twist, and Slug were assessed by RTq-PCR, whereas the β-catenin protein expression was also determined by immunocytochemistry. ILO (p < 0.05) and TMZ (p < 0.01) significantly inhibited the growth of U-87MG cells at all tested doses. The combination of 60 µM of both drugs showed synergistic activity with CDI < 1. The inhibition of migration and apoptosis was more pronounced in the case of combination treatment (p < 0.001). Inhibition of the invading cells was also found to be significant in ILO- and combination-treated groups (p < 0.001). ILO and combination treatment also significantly downregulated the expression of DRD2, while TMZ upregulated the expression (p < 0.001). The expressions of β-catenin (p < 0.001), Dvl2 (p < 0.001), Twist (p < 0.001), and Slug (p < 0.001) were also significantly downregulated in all treatment groups as compared to the vehicle control. The data suggest that ILO possesses strong growth inhibitory activity, possibly due to its effect on DRD2 and β-catenin expression and has the potential to be repurposed against GBM.

Objectives: To observe the cellular diameter of proximal convoluted tubules of kidney of albino rats on celecoxib induced kidney with protection by lycopene. Study Design: Experimental study. Setting: BMSI (Anatomy Department), JPMC, Karachi. Period: 4th May 2015 to 3rd June 2015. Materials and Methods: Ninety to one twenty days old, forty healthy adult, male Albino rats of 200-220gm were taken for the study. The rats were divided into 4 groups, Group A was control group, Group B receive Celecoxib 50 mg/kg body weight orally, Group C receive Celecoxib 50 mg/kg body weight orally along with lycopene50 mg/kg body weight orally and Group D receive lycopene 50 mg/kg body weight orally for 30 days. At the end of study rats were sacrificed and renal tissue sections were stained with hematoxylin and eosin. Results: Markedly increased cellular diameter of proximal convoluted tubules was observed in rats taking celecoxib. Slides stained with hematoxylin and eosin showed altered and degenerative changes in the renal parenchyma of cortex and medulla. Ballooning of cells, hemorrhage and moderate edema was seen in celecoxib group. Renal interstitium showed infiltration of mononuclear cells, congested and dilated blood vessels. However, renal architecture was improved and reversed in celecoxib along with lycopene receiving group. Conclusion: This study concludes that lycopene decreased the cellular diameter of proximal convoluted tubules in celecoxib treated group.