Tumor apoptosis induced by ruthenium(II)-ketoconazole is enhanced in nonsusceptible carcinoma by monoclonal antibody to EGF receptor

International Journal of Cancer. Journal International Du Cancer
M Strasberg RieberM Rieber

Abstract

Ketoconazole (KTZ) has been used as a second-line agent in hormone-refractory cancer therapy. Since transition metal complexes including those of Ru(III), show important anticancer activity with limited toxicity, we investigated the potential antitumor efficacy of Ru(II) complexed to KTZ or clotrimazole (CTZ) compared to Ru(II) alone or uncomplexed azoles. RuCl2(KTZ)2 exerted greater apoptosis- associated caspase-3 activation than RuCl2(CTZ)2, KTZ, CTZ or RuCl2(MeCN)4 against several human tumor cell monolayers. PARP cleavage and a decrease in S+G2 cells were evident after RuCl2(KTZ)2 treatment in genetically matched C8161 melanoma monolayers with unequal p53 functional status. Release of mitochondrial cytochrome c and Mn-SOD suggest mitochondria as a target of RuCl2(KTZ)2. Treatment of WM164 melanoma monolayers with 25 microM of cisplatin or RuCl2(KTZ)2 showed that the latter is more effective than cisplatin at inducing PARP fragmentation and proapoptotic Bak expression. Such results suggest that these Ru(II) and Pt(II) metal complexes are unequally effective and act through alternative signaling pathways. In studies with multicellular spheroids, which frequently are more resistant to cytotoxic anticancer drugs than monolayers...Continue Reading

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Citations

Feb 29, 2008·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Alberto MartínezRoberto A Sánchez-Delgado
Dec 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·Manuel Rieber, Mary Strasberg Rieber
Nov 26, 2013·Cell Biology and Toxicology·Elisa Robles-EscajedaRenato J Aguilera
Jun 2, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Alberta Bergamo, Gianni Sava
Dec 7, 2007·International Journal of Radiation Biology·Juergen FriedrichLeoni A Kunz-Schughart
Sep 10, 2005·International Journal of Cancer. Journal International Du Cancer·Manuel Rieber, Mary Strasberg Rieber
Oct 8, 2016·Organic & Biomolecular Chemistry·Harikrishna BavireddiRaghavendra Kikkeri
Mar 25, 2017·International Journal of Cancer. Journal International Du Cancer·Lluis Lopez-BarconsC Patrick Reynolds
Jun 12, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Radosław StarostaAnna Krasowska
Nov 9, 2019·Scientific Reports·Rodrigo F M de AlmeidaRadosław Starosta

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