Investigation of the effects of the antipsychotic drug Chlorpromazine on nitric oxide synthesis activity in the T98-G human glioblastoma cell line as a potential anticancer mechanism of action

Date

2024-12-06

Author

Polat, Janset Mehlika

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Chlorpromazine is an antipsychotic drug that is used in the treatment of schizophrenia and other various psychiatric disorders and draws attention with its anti-cancer properties. Studies have shown that this drug has an anti-cancer effect on different types of cancer through different mechanisms. Glioblastoma Multiforme is the most common central nervous system primary tumor that has currently no cure. The methods used for treatment in the disease process are not effective enough due to the plasticity caused by the high heterogeneity of the tumor. It is common and important to repurpose the drugs that have passed clinical stages for the treatment of cancers including Glioblastoma Multiforme for early intervention and increasing the life expectancy of patients. Studies show that nitric oxide synthase enzymes and, accordingly, nitric oxide levels are increased in Glioblastoma Multiforme. This increase often causes worse prognosis of the disease and a decrease in patient survival time. However, the effects of Chlorpromazine on nitric oxide levels and nitric oxide synthase expression, which have the potential to be targeted in Glioblastoma Multiforme, are not yet fully known. The aim of this thesis is to investigate how Chlorpromazine affects nitric oxide synthase expression and nitric oxide levels in the T98-G human glioblastoma cell line. For this purpose, the effect of chlorpromazine on T98-G cell proliferation and the drug concentration that inhibits 50% cell growth (IC50) was determined with the Resazurin Assay. Then, the effects of Chlorpromazine on the protein expression levels of nitric oxide synthase enzymes (iNOS and nNOS) were determined by Western Blotting. Chlorpromazine’s impacts on the gene expression levels of iNOS and nNOS were assessed by Quantitative Real-Time PCR, and the nitric oxide levels in the T98-G cell line was investigated by NO Assay. It was found that even though iNOS and nNOS levels increased at both protein and gene expression levels after CPZ treatment, the increase was not significant.

Subject Keywords

Chlorpromazine, Glioblastoma, Nitric oxide synthase, Nitric oxide

URI

https://hdl.handle.net/11511/113030

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Graduate School of Natural and Applied Sciences, Thesis