Trisenox induces cytotoxicity through phosphorylation of mitogen‐activated protein kinase molecules in acute leukemia cells

Abstract

Trisenox (TX) has been used successfully for the treatment of acute promyelocytic leukemia (APL) patients. TX –induced cytotoxicity in APL cells remains poorly understood. In this research, we investigated the molecular mechanism of TX cytotoxicity using APL cell lines. We assessed TX toxicity by quantitatively measuring lactate dehydrogenase (LDH) levels. Inhibition of cell cycle progression was assessed by confocal microscopy of Ki67 expression. Apoptosis was evaluated by western blot analysis of apoptotic proteins expression, immunocytochemistry, and confocal imaging of annexin V and propidium iodide. MAPK signaling cascade was analyzed by western blotting and inhibitor (based experiments with APL cells. We found that TX (induced cytotoxicity inhibited APL cell cycle progression. TX also induced significant (p<0.05) changes in the expression levels of apoptotic molecules, and activated the phosphorylation of MAPK signaling pathways in APL cells. Understanding the mechanism of TX cytotoxicity would be help in the design of new APL drugs.

p53 as a unique target of action of cisplatin in acute leukaemia cells

“…In brief, both control and CDDP‐treated cells were washed with ice cold PBS and incubated 15 min in mixture of annexin V and PI at room temperature. After incubation, cells were washed with 1X binding buffer and apoptosis analysed using the Cellometer Vision CBA/confocal microscopy (Fluoview 10i, Olympus), as previously described 33 …”

“…After incubation, cells were washed with 1X binding buffer and apoptosis analysed using the Cellometer Vision CBA/confocal microscopy (Fluoview 10i, Olympus), as previously described. 33…”