engleski

Diazene JK-279 induces apoptosis-like cell death in human cervical carcinoma cells

Diazene N-phenyl-2-(2-pyridinyl)diazenecarboxamide (JK-279) is a newly synthesized compound, cytotoxic for several tumor cell lines and their drug-resistant sublines. In human cervical carcinoma cells (HeLa), this compound reduced intracellular glutathione content and increased sensitivity to cisplatin. The aim of the present study was to elucidate the molecular mechanisms involved in cytotoxic effect of diazene JK-279 on HeLa cells. Cytotoxicity was determined by MTT method. Flow cytometry analysis showed that diazene JK-279 induces G2/M phase arrest. It was mediated by the increase in p21 expression, and accompanied by alteration in expression of survivin. The highest concentration of JK-279 altered nuclear morphology in intact cells, showing "apoptosis-like" features. No cleavage of procaspase-3, procaspase-9 and PARP, or altered expression of apoptotic proteins Bcl-2 and Bax were detected. At the same time, PS externalization and internucleosomal DNA cleavage were observed. Partially necrosis was detected as well. Our results demonstrated that cytotoxicity of diazene JK-279 is mostly the consequence of a caspase-independent cell death, which is in some aspects “ apoptosis-like” . Taking into account the multiplicity of mechanisms used by cancer cells to prevent apoptosis, the drugs (like diazene JK-279) that would activate alternative cell death pathways could provide a useful tool for new therapies of cancers.

diazenes; tumor cells; anti-cancer drugs; apoptosis-like cell death; caspase-independent cell death

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