ABSTRACT
Copper and zinc are the elements with numerous physiological activities. Copper [Cu] has an important role in angiogenesis and acts by increasing Vascular Endothelial Growth Factor [VEGF]. Serum levels of copper will be increased in cancer incidence, progression and recurrence. The aim of this study was to measure blood levels of copper, zinc, and the ratio of Cu /Zn, as well as VEGF levels before and after treatment of acute myeloid leukemia. Thirty patients who were recently diagnosed with Acute Myeloblastic Leukemia [AML] in Shahid Ghazi Tabatabai oncology hospital enrolled in this clinical trial. On the first day, blood samples were taken for copper, zinc, and VEGF assay and flowcytometry. Treatment protocol was [7x3] regimen. Blood samples were collected for evaluation of copper, zinc, and VEGF. They were sent to Biochemistry Laboratory in medicine faculty for analysis. Amongst 30 AML patients, 14 [46.7%] were female and 16 [53.3%] were male. Patients of various ages ranged from 16 to 53 years, with a median age of 9.1 +/- 9.35 years. The mean serum level of copper, zinc, and mean Cu/Zn ratio before and after treatment showed significant difference [p<0.05] There was also significant difference between the mean VEGF level before and after treatment [p<0.05]. This study reveals that there is no significant relationship between copper, zinc serum levels, their ratio, and VEGF in AML patients. We hypothesize that increased serum copper is associated with increase of VEGF levels which can indicate the impact of copper in malignancies including AML
ABSTRACT
Leukemia is a malignant disorder of the blood progenitor/stem cells which is characterized by abnormal proliferation of white blood cells. Although anti-cancer drugs induce apoptosis in cancerous cells, drug resistance is the significant problem mainly due to over-expression of inhibitors of apoptosis proteins [lAPs] such as survivin. In this content, it has been reported that an anti-inflammatory drug, Carbenoxolone [CBX], could induce apoptosis and growth inhibition in several types of cancerous cells. In the present study, effects of CBX on apoptosis and level of the expression of survivin gene and its deltaEx3 splicing variant have were evaluated in K562 cells. K562 cells were cultured and treated with different concentrations of CBX: [50-300 microM] at different time intervals [12-48 hrs]. Trypan blue exclusion test was used to evaluate cell viability. Fluorescent microscopy [Acridine Orange/Ethidium Bromide double staining] and DNA fragmentation assay were used to study apoptosis. The expression level of survivin and its deltaEx3 splice variant were studied by RT- PCR. It was found that both growth inhibition and apoptosis occurred in K562 cells. In addition, down-regulation of survivin and survin-deltaEx3 were observed, after 2-4 hrs treatment with 150 microM of CBX. However, the expression level of survivin and its deltaEx3 splice variant increased in subsequent time [6-12 hrs] nearly to the level of control cells. From the results of this study, it may be concluded that CBX can be considered as a candidate for further studies in CML treatment, especially in the case of drug- resistant leukemia cells