ABSTRACT
Nucleostemin [NS], a stem cell-abundant nucleolar protein, is critical for maintaining the self-renewal and proliferative properties of normal and cancerous stem cells. Recent data suggests that NS signaling is important for proliferation of T-cells and leukemia cells. This study was conducted to verify the role of NS in pathogenesis and treatment of T-cell acute lymphocytic leukemia [T-ALL]. Our results revealed that RNA interference-mediated NS silencing primarily affected clonogenicproperty of T-ALL cells by limiting their self-renewal potential in vitro.These effects were accompanied with inhibition of proliferation and early apoptosis in Jurkat cells [p53-null] while late apoptosis in Molt-4 [p53 functional] T-ALL cells. Collectively, our results suggest that NS is a critical regulator in self-renewal and apoptosis of different T-ALL cells. This suggests therapeutic potential of this gene in leukemia
ABSTRACT
Because drug resistance is one of the most important problems in patients with chronic myeloid leukemia [CML], finding new anti-cancer drugs especially from natural sources is research priority. Therefore, in this study, anti-cancer effects of ethyl acetate soluble metabolite of Iranian native bacteria, Streptomyces calvus, were studied using human chronic myeloid leukemia K562 cells. In this experimental trail, ethyl acetate soluble metabolites were isolated from S. calvus bacteria. K562 cell line was treated by various concentrations of this metabolite for 12- 72 h intervals. Anti-proliferative effects of ethyl acetate soluble metabolite were studied by trypan blue exclusion test. Wright-Giemsa staining and latex particle phagocytosis assay were used to study differentiated cells. Ethyl acetate soluble metabolite induced growth inhibition in K562 cells in concentration and time- dependent manner. At the concentration of 200 ng/ml, the growth was inhibited 19-50% after 12-72h. Latex particle phagocytosis assay and Wright- Giemsa staining results revealed that K562 cells were differentiated toward monocytic- macrophagic lineage. According to growth inhibitory and differentiating effects of S.calvus metabolite in K562 cells, this metabolite can be proposed for more investigations in differentiation therapy of CML patients.