Anti-leukemic activity of phosphoproteins from Sesamin via induction of nuclear antigen H731and CLIP-associating protein 2 isoform X25 mediated apoptosis

Leukemia is an uncontrolled proliferation hematopoietic cancer cells that commonly treats with conventional therapies such as chemotherapy. However, many side effects were reported. Alternative medicines have been developed by using natural or herb compounds as therapeutic drug. Sesamin, a class of phytoestrogen isolated from sesame seed displaying potent anticancer activity in vitro and in vivo.However, the mechanism by which sesamin mediates anticancer effects on leukemic cells are notfully understood. In thisstudy, the effects of sesamin on cell viability, cell apoptosis and expression of phosphoproteins in Molt-4 and NB4 leukemic cell lines were investigated using MTT assay, flow cytometry and immobilized metal affinity chromatography (IMAC) phosphoprotein enrichment and LC-MS, respectively. The results showed that sesamin reduced viability and induced apoptosis in leukemic cells. In addition, 79 phosphoproteins were identified from LC-MS within three main clusters including biological regulation, cellular processand metabolic process. Interestingly, nuclear antigen H731 (PDCD4) and CLIP-associating protein 2 isoform X25 (CLASP2) showed increased in sesamin treated cells and associated protein-ligand interaction network with allicin, capsaicin, cucurbitacin B, and rapamycin which are known to activate apoptosis in cancer cells.Then, sesamin could be developed as candidate of alternative leukemia treatment  in the future

Effect of Tumor Necrosis Factor-Alpha on Erythropoietinand Erythropoietin Receptor-Induced Erythroid Progenitor Cell Proliferation in β Thalassemia/Hemoglobin E Patients

Objective: Thalassemia is one of the genetic diseases that cause anemia and ineffective erythropoiesis. Increased levels of several inflammatory cytokines have been reported in β thalassemia and might contribute to ineffective erythropoiesis. However, the mechanism by which tumor necrosis factor-alpha (TNF-α) is involved in ineffective erythropoiesis in thalassemic patients remains unclear. The objective of this study is to investigate the effect of TNF-α on the erythropoietin (EPO) and erythropoietin receptor (EPOR) expression involved in proliferation of β-thalassemia/hemoglobin (Hb) E erythroid progenitor cells compared with cells from healthy subjects. Materials and Methods: CD34-positive cells were isolated from heparinized blood by using the EasySep® CD34 selection kit. Cells were then cultured with suitable culture medium in various concentrations of EPO for 14 days. The effect of TNF-α on percent cell viability was analyzed by trypan blue staining. In addition, the percentage of apoptosis and levels of EPOR protein were measured by flow cytometry. Results: Upon EPO treatment, a higher cell number was observed for erythroid progenitor cells from both healthy participants and β-thalassemia/Hb E patients. However, a reduction of apoptosis was found in EPO-treated cells especially for β-thalassemia/ Hb E patients. Interestingly, TNF-α caused higher levels of cell apoptosis and lower levels of EPOR protein in thalassemic erythroid progenitor cells. Conclusion: TNF-α caused a reduction in the level of EPOR protein and EPO-induced erythroid progenitor cell proliferation. It is possible that TNF-α could be involved in the mechanism of ineffective erythropoiesis in β-thalassemia/Hb E patients