MPA increases idarubicin-induced apoptosis in chronic lymphatic leukaemia cells via caspase-3 |
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Authors: | Florio Salvatore Crispino Luca Ciarcia Roberto Vacca Giovanni Pagnini Ugo de Matteis Andrea Pacilio Carmen D'Andrilli Giuseppina Kumar Christine Giordano Antonio |
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Institution: | Department of Structures, Functions and Biological Technologies, School of Veterinary Medicine, University of Naples Federico II, Naples, Italy. |
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Abstract: | The caspase family of protease is speculated to have a crucial role in apoptosis. The effect of treatment with Idarubicin (IDA) and Medroxyprogesterone acetate (MPA), used alone or in combination, on the activation of Caspase-3 in canine Chronic Lymphatic Leukaemia (CLL) cells was investigated, in order to clarify the mechanism of chemo- and hormone-therapy mediated apoptosis. Caspase activity was determined by a quantitative fluorimetric assay. Apoptosis was monitored by propidium iodide (PI) and nucleosomes assay. Treatment of CLL cells for 24 h with MPA 5 microM did not significantly activate caspase-3 but its activity was increased almost 5-fold more with IDA 1 microM (P < 0.05) than control. Treatment of CLL cells with IDA 1 microM in equimolecular association with MPA was able to increase the activation of caspase-3 induced by IDA of the 61.2% (P < 0.05) in comparison with IDA alone. The activation of caspase-3 was confirmed evaluating apoptosis by PI and nucleosomes assay. Furthermore, both caspase-3 activation and apoptosis triggered by IDA alone or in combination with MPA were significantly inhibited by specific caspase-3 inhibitor AC-DEVD-CMK. These findings provide an explanation for IDA and MPA induced-apoptosis mechanism. |
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Keywords: | idarubicin medroxyprogesterone acetate apoptosis caspase‐3 |
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