"The Effect of Arylhydrazone of Active Methylene Compounds on GBM Cell Lines"
Kute, Dinesh Sunil (2021)
Kute, Dinesh Sunil
2021
Master's Programme in Biomedical Technology
Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology
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Hyväksymispäivämäärä
2021-05-20
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202104273911
https://urn.fi/URN:NBN:fi:tuni-202104273911
Tiivistelmä
Glioblastoma (GBM), a WHO grade IV glioma, is the most common and one of the malignant types of central nervous system tumors in adults. The resistance of GBM cells to antineoplastic agents has been the biggest obstacle in the treatment of GBM tumors. The temozolomide, a frontline GBM chemotherapy drug, has increased the median survival of the patients approximately for one and a half years only. Therefore, there is a need for the development of a novel anti-GBM drug that increases the median survival of the GBM patients with fewer side effects. The hydrazone derivatives inhibit the growth and proliferation of GBM tumors. In this study, arylhydrazone of active methylene compounds (AHAMCs) was examined using GBM cell lines U87 and LN229. The antitumor activity of AHAMC compound R234 was investigated by performing cytotoxic assay and dose- and time-dependent assay. To ascertain whether the R234 compound obstructs the cell cycle progression, GBM cells were stained with the propidium iodide (PI) dye and analyzed using cellProfiler software. To improve the quality of the segmentation several combinations of thresholding strategies and thresholding methods were tested for both the cell lines. The global and adaptive thresholding strategies and Otsu’s and maximum correlation thresholding (MCT) methods that returned comparable segmentation results were selected. Further, segmentation results of the selected thresholding strategies and methods were compared by calculating the false negatives (FN) and false positives (FP) for each combination manually. Finally, the segmentation results obtained from the combination of global strategy and MCT method were chosen for the intensity measurement. The cells were then grouped into the different phases of the cell cycle from the histogram of PI intensities. The proportions of the cells in each phase of the cell cycle show that the R234 arrests the cell cycle at the G2/M phase in both cell lines. Overall, the results suggest that the R234 compound exerts its cytotoxic activity by arresting the cell cycle at the G2/M phase.