Ruthenium polypyridyl complexes that induce mitochondria-mediated apoptosis in cancer cells.
ABSTRACT The limitations of cisplatin-based chemotherapy, including high toxicity, undesirable side effects, and drug resistance, have motivated extensive investigations into alternative metal-based cancer therapies. Ruthenium (Ru) possesses several favorable properties suited to rational anticancer drug design and biological applications. In the present study, we synthesized a series of ruthenium polypyridyl complexes containing N,N-chelating ligands, examined their anticancer activities, and elucidated the molecular mechanisms through which they caused the cancer cell death. The results demonstrated that [Ru(phen)(2)-p-MOPIP](PF(6))(2).2H(2)O (RuPOP), a complex with potent antiproliferative activity, is able to induce mitochondria-mediated and caspase-dependent apoptosis in human cancer cells. On the basis of these results, we suggest that RuPOP may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially for melanoma.
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ABSTRACT: Organometallic half-sandwich complexes [M(p-cymene)(azo/imino-pyridine)X](+) where M = Ru(II) or Os(II) and X ═ Cl or I, exhibit potent antiproliferative activity toward a range of cancer cells. Not only are the iodido complexes more potent than the chlorido analogues, but they are not cross-resistant with the clinical platinum drugs cisplatin and oxaliplatin. They are also more selective for cancer cells versus normal cells (fibroblasts) and show high accumulation in cell membranes. They arrest cell growth in G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. The iodido complexes retain potency in p53 mutant colon cells. All complexes activate caspase 3. In general, antiproliferative activity is greatly enhanced by low levels of the glutathione synthase inhibitor l-buthionine sulfoxime. The work illustrates how subtle changes to the design of low-spin d(6) metal complexes can lead to major changes in cellular metabolism and to potent complexes with novel mechanisms of anticancer activity.Journal of Medicinal Chemistry 01/2013; · 5.61 Impact Factor
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ABSTRACT: The first-year students’ attitudes related to teaching are necessary teleological landmarks for choosing this career. This study has two. The main objectives of this study were to determine the level of cultural intelligence of teachers and to examine which variables could be considered as predictors of cultural intelligence. The study involved 107 elementary school teachers (86.9% female and 13.1% male) from four towns in Serbia. The results show that teachers demonstrate a high level of cultural intelligence and that significant predictors of teachers’ cultural intelligence are enjoyment of intercultural communication, experiencing multicultural classes as a challenge, openness to cultural learning and contacts with people from other cultures. The implications of these results for teachers’ education are presented.Procedia - Social and Behavioral Sciences 01/2011; 11:276-280.