The ruthenium(II)–arene compound RAPTA-C induces apoptosis in EAC cells through mitochondrial and p53–JNK pathways |
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Authors: | Soumya Chatterjee Subhadip Kundu Arindam Bhattacharyya Christian G Hartinger Paul J Dyson |
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Institution: | (1) Department of Environmental Science, University of Kalyani, Kalyani, India;(2) Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland |
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Abstract: | An investigation of the molecular mechanism of the anticancer activity demonstrated by the ruthenium(II)–arene compound Ru(η6-p-cymene)Cl2(pta)] (pta is 1,3,5-triaza-7-phosphaadamantane), termed “RAPTA-C”, in Ehrlich ascites carcinoma (EAC) bearing mice is described.
RAPTA-C exhibits effective cell growth inhibition by triggering G2/M phase arrest and apoptosis in cancer cells. Cell cycle arrest is associated with increased levels of p21 and reduced amounts
of cyclin E. RAPTA-C treatment also enhances the levels of p53, and its treatment triggers the mitochondrial apoptotic pathway,
as shown by the change in Bax to Bcl-2 ratios, resulting in cytochrome c release and caspase-9 activation. c-Jun NH2-terminal kinase (JNK) is a critical mediator in RAPTA-C-induced cell growth inhibition. Activation of JNK by RAPTA-C increases
significantly during apoptosis. Overall, these results suggest a critical role for JNK and p53 in RAPTA-C-induced G2/M arrest and apoptosis of EAC-bearing mice. Consequently, RAPTA-C treatment results in a significant inhibition in the progression
of cancer in an animal model, which emulates the human disease, and does so with remarkably low general toxicity; hence, RAPTA-C
has potential for clinical application. |
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Keywords: | Anticancer research Apoptosis Bioorganometallics p53 Ruthenium |
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