engleski

New N-9-sulfonylpurine derivatives induce changes in mitochondrial function and ROS accumulation in carcinoma and leukemia cells in vitro

Our recent studies showed significant antiproliferative capa city of newly synthesized N-9-sulfonylpyrimidine derivatives on human carcinoma, lymphoma, and leukemia cells. These derivatives behave as antimetabolites exploiting cellular metabolism to induce cytotoxicity in treated tumors’ cells (1 -3). Based on prev iously obtained results on N-9-sulfonylpyrimidine derivatives, a new series of N-9-sulfonylpurine derivatives were synthesized and tested on biological potential. The aim of this study was to determine if measured antitumor activity of N-9-sulfonylpurine derivatives is linked with ROS accumulation and mitochondrial membrane destabilization in human cervix adenocarcinoma (HeLa), human chronic myelogenous leukemia (K562) and human Burkitt’s lymphoma (Raji) cells. Changes in the mitochondrial membrane potential (∆Ψm) of tested compounds were determined by flow cytometry, measuring fluorescence of JC-1 dye in tumor cells after 24 hours of treatment. Intracellular accumulation of ROS was determined after 1 hour in cells exposed to N-9-sulfonylpurine derivatives by flow cytometry as well. Tested derivatives induced increased accumulation of ROS and mitochondrial disruption in more than 80% of HeLa and Raji cells. The effect of tested derivatives on K562 cells is reflected by the change of mitochondrial potential in more than 70% with slightly reduced accumulation of ROS. Based on obtained results we can conclude that newly synthesized N-9-sulfonylpurine derivatives are good candidates for further antitumor studies.

carcinoma cells, leukemia cells, ROS, mitochondrial membrane potential

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