The drug 6-thioguanine (6-TG) is one of the thiopurines successfully used in oncology, especially for acute myeloid leukemia (AML). It is proposed to act as an epigenetic drug affecting DNA methylation. The aim of this study was to clarify the effect of 6-TG on the proliferation, viability and expression of genes coding for the enzymes DNA methyltransferase 3A and DNA methyltransferase 3B (DNMTs) as well as histone deacetylase 3 (HDAC3) and histone deacetylase 7 (HDAC7) in the human promyelocytic AML cell line HL60.
In this experimental study, HL60 cells and also normal peripheral blood mononuclear cells (PBMCs) were grown in RPMI 1640 medium containing 10% fetal bovine serum. They were then treated with 6-TG at their exponential growth phase. Cell viability was monitored using the Cell Counting Kit-8 assay with an enzyme-linked immunosorbent assay (ELISA) reader. The expressions of the above mentioned 4 genes were quantified using real-time PCR.
6-TG could inhibit the proliferation of HL60 cells and decrease their viability. In HL60 cells, as compared to normal PBMCs, 6-TG significantly decreased HDAC3 (p = 0.0034) as well as DNMT3B (p = 0.03) and HDAC7 (p = 0.0031) gene expressions, but increased the expression of DNMT3A gene (p = 0.16) after normalization to GAPDH as the housekeeping gene.
These findings suggest that the altered expression of DNMT3A, DNMT3B, HDAC3 and HDAC7 genes is responsible for at least part of the antitumor properties of 6-TG, providing an insight into the mechanism of its action as an epigenetic drug.
Background: Kidney function test (KFT) is a routine laboratory examination used in the diagnosis of many disorders, the kidney participates in several essential functions in the human body, and kidney dysfunction can lead to morbidity and mortality. Therefore, studying the levels of KFT in early diagnosed cancer patients can identify how the kidney perform when cancer begins, and which parameter of KFT is affected early.
Objective: This study aimed to evaluate levels of kidneys function profile including blood urea, creatinine, sodium (Na), potassium (K), and chloride in untreated cancer patients.
Patients and methods: 211 participants including 44 healthy controls and 167 patients diagnosed as early cancer were enrolled in this study in Taif city, and this study was performed at King Faisal Hospital (KFH) and Taif University. Serum levels of blood urea, creatinine, sodium (Na), potassium (K), and chloride were analyzed. The total number of patients was 167 and healthy controls were 44. Types of cancer in the patients included in this study were 49 breast cancer, 45 gastrointestinal tract cancer, 39 gynecological tumors, 17 head and neck cancer and 17 respiratory cancer. Statistical assessment was done by applying T-test, Chi-square, odds ratio.
Results: Sodium, potassium, creatinine and chloride levels were significantly higher in cancer patients compared to the healthy controls and the urea was normal and nothing was significant.
Conclusion: Most common electrolytes abnormality increased in our study group of cancer patients. A sudden death could be resulted when the potassium level increased rapidly. Dysregulation in urea, chloride and creatinine could be a cancer marker and lead to fatal problems.