Abstract
Ru(II)-thymine complex [Ru(PPh3)2(Thy)(bipy)]PF6 (where PPh3 = triphenylphosphine, Thy = thyminate and bipy = 2,2'-bipyridine) is a potent cytotoxic agent with ability to bind to DNA, inducing caspase-mediated apoptosis in leukemia cells. In this study, we investigated the mechanism underlying the cell death induction by Ru(II)-thymine complex in human colon carcinoma HCT116 cells, as well as its effect in xenograft tumor model. The Ru(II)-thymine complex increased significantly the percentage of apoptotic HCT116 cells. Co-treatment with a JNK/SAPK inhibitor, p38 MAPK inhibitor and MEK inhibitor, which inhibit the activation of ERK1/2, caused a marked reduction of the percentage of complex-induced apoptotic cells. Moreover, the Ru(II)-thymine complex induced an increase in phospho-JNK2 (T183/Y185), phospho-p38α (T180/Y182) and phospho-ERK1 (T202/Y204) levels in HCT116 cells. Treatment with the Ru(II)-thymine complex increased significantly the phospho-histone H2AX (S139) expression, a DNA damage marker. The expression of phospho-p53 (S15) and MDM2 were not changed, and the co-treatment with a p53 inhibitor (cyclic pifithrin-α) did not reduce the complex-induced apoptosis in HCT116 cells, indicating that the Ru(II)-thymine compl...Continue Reading
References
Sep 20, 2000·The Journal of Biological Chemistry·X WangN J Holbrook
Feb 14, 2007·Oncogene·Y YanK H Cowan
Jul 4, 2008·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Soumya ChatterjeePaul J Dyson
Feb 12, 2009·Anti-cancer Drugs·Frederike LentzUNKNOWN Central European Society for Anticancer Drug Research-EWIV
Jul 20, 2010·Cellular Signalling·Fengxiang WeiDamu Tang
Jul 5, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Gianni SavaPaul J Dyson
Feb 25, 2014·FEBS Letters·Vikash SinghRaghuvir S Tomar
Oct 24, 2014·Annual Review of Medicine·Kristen K CiomborRichard M Goldberg
Oct 26, 2014·Investigational New Drugs·Suzanne LeijenJan H M Schellens
Feb 19, 2015·Archives of Toxicology·Eun Kyung Kim, Eui-Ju Choi
May 14, 2016·Molecular Pharmaceutics·Mun Juinn ChowWee Han Ang
Nov 5, 2016·Oncotarget·Lanmei ChenBilian Xu
Nov 27, 2016·Oncotarget·Karin HientzThomas Efferth
Mar 25, 2017·Biomaterials·Zhiqin DengTianfeng Chen
Apr 27, 2017·European Journal of Medicinal Chemistry·Tatjana LazarevićŽivadin D Bugarčić
May 27, 2017·The FEBS Journal·Simon J CookMatthew J Sale
Sep 15, 2017·Oncotarget·Isabelle CorreJacques Huot
Sep 19, 2017·Thoracic Cancer·Seung Soo YooJae Yong Park
Dec 14, 2017·Genes & Cancer·Danny N Dhanasekaran, E Premkumar Reddy
Dec 21, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jincan ChenLanmei Chen
Dec 22, 2017·Oncotarget·Cinara O D'Sousa CostaDaniel P Bezerra
Jan 13, 2018·Scientific Reports·Valdenizia Rodrigues SilvaDaniel Pereira Bezerra
Jan 25, 2018·Cell Death & Disease·Nanashara C de CarvalhoDaniel P Bezerra
Feb 16, 2018·Journal of Medicinal Chemistry·Sreekanth ThotaEliezer J Barreiro
Apr 4, 2018·The Lancet Oncology·Timothy J IvesonJames Paul
Jun 1, 2018·International Journal of Molecular Sciences·Maiara de Souza OliveiraDaniel Pereira Bezerra
Jul 27, 2018·European Journal of Medicinal Chemistry·Baskaran PurushothamanJoon Myong Song
Sep 13, 2018·CA: a Cancer Journal for Clinicians·Freddie BrayAhmedin Jemal
Sep 25, 2018·Journal of Cellular Physiology·Souvik RoyTania Chakraborty
Oct 20, 2018·Cancer Letters·Vania VidimarChristian Gaiddon
Oct 26, 2018·Redox Biology·Maiara de S OliveiraDaniel P Bezerra
Citations
Jul 25, 2020·BMC Cancer·Khayal Al-KhayalRehan Ahmad
Apr 4, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Felipe Pantoja MesquitaRaquel Carvalho Montenegro
Dec 29, 2020·Chemistry : a European Journal·Sofia I BärRainer Schobert
May 1, 2021·International Journal of Molecular Sciences·Marta Orts-ArroyoJosé Martínez-Lillo
May 12, 2021·Inorganic Chemistry·Oscar A Lenis-RojasBeatriz Royo
Jul 31, 2020·Journal of Ethnopharmacology·Talita A da AnunciaçãoDaniel P Bezerra
Feb 26, 2020·Inorganic Chemistry·Nicholas P ToupinJeremy J Kodanko
Aug 29, 2021·Pharmaceutics·Kazi Mustafa MahmudMd Asiful Islam