Imam Abdulrahman Bin Faisal University
Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/16
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Item Restricted Comparing the Effect of Two Pyrimidine Analogues on Colorectal Cancer Cells(2021) Alshammari, Thamer Marhoun Bin Jarbou; ثابت، حسين حسن; المفتي، سارة أمينNowadays, people are living in an era with high standards of healthcare accessibility, which can remarkably improve the diagnostic tools and the treatment plans of different diseases. These standards contribute to the determination of the general life expectancy in many parts of the world. With cancer, however, the mortality rate has globally increased by almost 40% over the past four decades, and it is expected that the mortality will further increase to reach 60% in the current decade with an estimated death of 13 million cancer patients by the year 2030. Colorectal cancer (CRC) is considered the third most frequent type of cancer and the second leading cause of cancer-related deaths, for both sexes, in the world. The explanation of the increased mortality of colorectal cancer might be due to some environmental factors, such as; smoking, bad diet, obesity, and very low physical activity, in addition to genetic background. The major pathways of either environmental (epigenetic) or genetic causes of CRC include CpG hypermethylation and microsatellite instability (MSI) due to the mismatch repair (MMR) gene deficiency. Considering that CRC accounts for 10% of the most commonly diagnosed types of cancer, there is an urgent need for developing effective treatment plans for CRC patients. 5-Azacytidine (5-AZA), a cytidine pyrimidine nucleoside analogue, is an epigenetic drug that incorporates into DNA and blocks the activity of the DNMT enzyme and thereby inhibits DNA methylation that might cause CRC. In addition to 5-AZA, another chemotherapeutic drug named 5-fluorouracil (5-FU) was applied either synergistically with 5-AZA, or alone, in this study. Both drugs were applied to the human colorectal carcinoma cell line, HCT116, by performing several methods, such as MTT assay, wound healing assay, and colony formation assay to assess the cells viability and migration property before and after treatment to analyse their effect on CRC. In addition, whole exome sequencing (WES) was performed to assess the genetic changes after treatment with 5-FU. HEK293, which is the human embryonic kidney cell line, was used in the study as the control cell line receiving the same treatment regime as the HCT116 cells. The main result of this study shows that both drugs have a noticeable effect on the viability of HCT116 cells. 5-AZA alone possesses the highest efficacy on HCT116 cells, followed by the drugs combination and 5-FU alone, respectively. In addition, WES results show that 5-FU diminished the number of mutations in HCT116 cells. In a conclusion, 5-AZA alone as a treatment plan for CRC has more efficacy than either 5-FU alone or the drugs combination which leads to the recommendation of using it alone as an anticancer drug. Also, WES results suggest that the 5-FU mechanism of action as a DNA damage drug is proven.8 0