Drug resistance of cancer cells is often correlated with the evasion of apoptosis, thus a major goal in cancer research is to search for compounds able to counteract cancer by promoting apoptosis. A variety of compounds with anticancer activity are characterised by the presence of the pyrazole as core nucleus. We synthesised a panel of pyrrolyl-pyrazole-carboxamides and we focused on the new compound RS 2780 (N2-phenylethyl 1-(4-chlorophenyl)-3-methyl-5-pyrrolylpyrazole-4-carboxamide). The biological effects of Rs 2780 on cell proliferation and viability were first evaluated on human HeLa cancer cells. As revealed by cell growth and viability experiments. a 24-h treatment of HeLa cells with increasing concentrations of RS 2780 (ranging from 0.1 to 100 mu M) proved to inhibit cell proliferation and to affect cell viability. Notably, the new compound was effective also on colon carcinoma SW613-B3 cells, which are extremely resistant to most drugs, while it does not alter the proliferation of normal fibroblasts. We observed that RS 2780 interferes with the structural and functional properties of mitochondria, leading to the activation of the mitochondria-dependent apoptotic pathway. Apoptosis occurrence was supported by a number of morphological and biochemical hallmarks, including chromatin condensation, internucleosomal DNA fragmentation, PARP-1 cleavage and caspase activation. In conclusion, our results demonstrate for the first time the anti proliferative properties of the new compound RS 2780 on HeLa and SW613-B3 cancer cells and show that its effects on mitochondria lead to apoptosis. (C) 2009 Elsevier Ltd. All rights reserved.

Study of the effects of a new pyrazolecarboxamide: Changes in mitochondria and induction of apoptosis / Vincenzo, Giansanti; Tania, Camboni; Piscitelli, Francesco; Ennio, Prosperi; LA REGINA, Giuseppe; Maria C., Lazze; Giada, Santin; Silvestri, Romano; Anna I., Scovassi. - In: THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY. - ISSN 1357-2725. - 41:10(2009), pp. 1890-1898. [10.1016/j.biocel.2009.04.008]

Study of the effects of a new pyrazolecarboxamide: Changes in mitochondria and induction of apoptosis

PISCITELLI, FRANCESCO;LA REGINA, GIUSEPPE;SILVESTRI, Romano;
2009

Abstract

Drug resistance of cancer cells is often correlated with the evasion of apoptosis, thus a major goal in cancer research is to search for compounds able to counteract cancer by promoting apoptosis. A variety of compounds with anticancer activity are characterised by the presence of the pyrazole as core nucleus. We synthesised a panel of pyrrolyl-pyrazole-carboxamides and we focused on the new compound RS 2780 (N2-phenylethyl 1-(4-chlorophenyl)-3-methyl-5-pyrrolylpyrazole-4-carboxamide). The biological effects of Rs 2780 on cell proliferation and viability were first evaluated on human HeLa cancer cells. As revealed by cell growth and viability experiments. a 24-h treatment of HeLa cells with increasing concentrations of RS 2780 (ranging from 0.1 to 100 mu M) proved to inhibit cell proliferation and to affect cell viability. Notably, the new compound was effective also on colon carcinoma SW613-B3 cells, which are extremely resistant to most drugs, while it does not alter the proliferation of normal fibroblasts. We observed that RS 2780 interferes with the structural and functional properties of mitochondria, leading to the activation of the mitochondria-dependent apoptotic pathway. Apoptosis occurrence was supported by a number of morphological and biochemical hallmarks, including chromatin condensation, internucleosomal DNA fragmentation, PARP-1 cleavage and caspase activation. In conclusion, our results demonstrate for the first time the anti proliferative properties of the new compound RS 2780 on HeLa and SW613-B3 cancer cells and show that its effects on mitochondria lead to apoptosis. (C) 2009 Elsevier Ltd. All rights reserved.
2009
apoptosis; cancer cell lines; mitochondria; proliferation; pyrazolecarboxamide
01 Pubblicazione su rivista::01a Articolo in rivista
Study of the effects of a new pyrazolecarboxamide: Changes in mitochondria and induction of apoptosis / Vincenzo, Giansanti; Tania, Camboni; Piscitelli, Francesco; Ennio, Prosperi; LA REGINA, Giuseppe; Maria C., Lazze; Giada, Santin; Silvestri, Romano; Anna I., Scovassi. - In: THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY. - ISSN 1357-2725. - 41:10(2009), pp. 1890-1898. [10.1016/j.biocel.2009.04.008]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/364409
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