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3044452 
Journal Article 
The ruthenium(II)-arene compound RAPTA-C induces apoptosis in EAC cells through mitochondrial and p53-JNK pathways 
Chatterjee, S; Kundu, S; Bhattacharyya, A; Hartinger, CG; Dyson, PJ 
2008 
Yes 
Journal of Biological Inorganic Chemistry
ISSN: 0949-8257
EISSN: 1432-1327 
13 
7 
1149-1155 
English 
18597125 
WOS:000259248900010 
An investigation of the molecular mechanism of the anticancer activity demonstrated by the ruthenium(II)-arene compound [Ru(eta(6)-p-cymene)Cl(2)(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 G(2)/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 NH(2)-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 G(2)/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. 
anticancer research; apoptosis; bioorganometallics; p53; ruthenium