Cell Cycle Arrest and Apoptosis Induction by a New 2,4-Dinitrobenzenesulfonamide Derivative In Acute Leukemia Cells

Abstract

Background: Current therapies for acute leukemias (ALs) are associated with severe adverse reactions and high relapse rates, which makes the search for new antileukemic agents a necessity. Therefore, the aim of this study was to evaluate the effects of a new sulfonamide, S1, in AL cells K562 and Jurkat. Methods: The cytotoxic activity of S1 was assessed using MTT method. The involvement of apoptosis in the mechanism of cell death was assessed by flow cytometry and fluorescence microscopy. Results: Our results demonstrated that S1 induced morphological changes suggestive of apoptosis in both K562 and Jurkat cells. Additionally, S1 was not cytotoxic to normal erythrocytes and mononuclear cells and had a highly selective cytotoxicity for AL lineages. The mechanisms of cell death induced by S1 in K562 cells involves cell cycle arrest at G2/M phase and the activation of both extrinsic and intrinsic apoptosis, with an increased FasR and AIF expression and the loss of mitochondrial potential. As for Jurkat, we observed cell cycle blockade at G0/G1 phase, phosphatidylserine exposure and the involvement of intrinsic apoptosis only, with mitochondrial potential loss and a reduced expression of Survivin. Although sulfonamide S1 did not altered Bcl-2 and Bax expression in AL cell lines, it was able to activate caspase-3 in K562 cells. Conclusion: Our results suggest that sulfonamide S1 may be a promising candidate for the development of new drugs for the treatment of ALs

Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages

“…D-Cyclins 1 and 2 (CCND1, CCND2) are key elements in the control of cell cycle progression from G1 to S phases [33,34]. It has been described that CCND1 overexpression is related with the arresting of cell proliferation [35].…”

Targeting Proliferation Signals and the Cell Cycle Machinery in Acute Leukemias: Novel Molecules on the Horizon

“…Compound 8 , carrying an N,N-dimethylamino ethoxyl moiety at the C-6 position, induced cell cycle arrest at the G0/G1 phase in HL-60 cells by suppressing the activation of AKT ( Figure 2 ) and S6K1, a serine/threonine kinase belonging to the mTORC1 pathway. A new 2,4-dinitrobenzenesulfonamide derivative (S1) triggered G0/G1 blockade, intrinsic apoptosis and reduction of Survivin expression in the Jurkat T-ALL model, while showing no cytotoxicity towards normal erythrocytes and mononuclear cells [ 120 ]. Analogs based on the fungi-derived polyenylpyrrole products rumbrin and auxarconjugatin-B (and in particular the octatetraenylpyrrole analog 3s ) were also able to suppress the proliferation of T-ALL cells [ 121 ].…”