Ru(II)-Thymine Complex Causes Cell Growth Inhibition and Induction of Caspase-Mediated Apoptosis in Human Promyelocytic Leukemia HL-60 Cells.

作者: Maiara de Souza Oliveira , Ádila de Santana , Rodrigo Correa , Milena Soares , Alzir Batista

DOI: 10.3390/IJMS19061609

关键词:

摘要: Ruthenium-based compounds represent a class of potential antineoplastic drugs. Recently, we designed, synthesized, and identified the Ru(II)-thymine complex [Ru(PPh3)2(Thy)(bipy)]PF6 (where PPh = triphenylphosphine, Thy thymine bipy 2,2′-bipyridine) as potent cytotoxic agent with ability to bind DNA human bovine serum albumins. In this study, underlying mechanism was assessed. This displayed cytotoxicity in different cancer cell lines; morphology that is associated apoptotic death, increased internucleosomal fragmentation without membrane permeability, loss mitochondrial transmembrane potential, phosphatidylserine externalization, caspase-3 activation were observed promyelocytic leukemia HL-60 cells treated complex. Moreover, pretreatment Z-VAD(OMe)-FMK, pan-caspase inhibitor, partially reduced apoptosis induced by complex, indicating death occurred through caspase-mediated pathway. conclusion, displays induces cells.

参考文章(28)
Manon van Engeland, Luc J.W. Nieland, Frans C.S. Ramaekers, Bert Schutte, Chris P.M. Reutelingsperger, Annexin V‐Affinity assay: A review on an apoptosis detection system based on phosphatidylserine exposure Cytometry. ,vol. 31, pp. 1- 9 ,(1998) , 10.1002/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R
Francesc X. Sureda, Elena Escubedo, Cec�lia Gabriel, Jaume Comas, Jorge Camarasa, Antonio Camins, Mitochondrial membrane potential measurement in rat cerebellar neurons by flow cytometry. Cytometry. ,vol. 28, pp. 74- 80 ,(1997) , 10.1002/(SICI)1097-0320(19970501)28:1<74::AID-CYTO9>3.0.CO;2-H
I. Nicoletti, G. Migliorati, M.C. Pagliacci, F. Grignani, C. Riccardi, A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry Journal of Immunological Methods. ,vol. 139, pp. 271- 279 ,(1991) , 10.1016/0022-1759(91)90198-O
Daniel Pereira Bezerra, Gardenia Carmen Gadelha Militão, Fernanda Oliveira de Castro, Cláudia Pessoa, Manoel Odorico de Moraes, Edilberto Rocha Silveira, Mary Anne Sousa Lima, Francisca Juliana Martins Elmiro, Letícia Veras Costa-Lotufo, Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways. Toxicology in Vitro. ,vol. 21, pp. 1- 8 ,(2007) , 10.1016/J.TIV.2006.07.007
Suzanne Leijen, Sjaak A. Burgers, Paul Baas, Dick Pluim, Matthijs Tibben, Erik van Werkhoven, Enzo Alessio, Gianni Sava, Jos H. Beijnen, Jan H. M. Schellens, Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy Investigational New Drugs. ,vol. 33, pp. 201- 214 ,(2015) , 10.1007/S10637-014-0179-1
Carl P. LeBel, Harry Ischiropoulos, Stephen C. Bondy, Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress Chemical Research in Toxicology. ,vol. 5, pp. 227- 231 ,(1992) , 10.1021/TX00026A012
L. Ouyang, Z. Shi, S. Zhao, F.-T. Wang, T.-T. Zhou, B. Liu, J.-K. Bao, Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis Cell Proliferation. ,vol. 45, pp. 487- 498 ,(2012) , 10.1111/J.1365-2184.2012.00845.X
Frederike Lentz, Anne Drescher, Andreas Lindauer, Magdalena Henke, Ralf A Hilger, Christian G Hartinger, Max E Scheulen, Christian Dittrich, Bernhard K Keppler, Ulrich Jaehde, Central European Society for Anticancer Drug Research-EWIV, Pharmacokinetics of a novel anticancer ruthenium complex (KP1019, FFC14A) in a phase I dose-escalation study. Anti-Cancer Drugs. ,vol. 20, pp. 97- 103 ,(2009) , 10.1097/CAD.0B013E328322FBC5
Hemerson I.F. Magalhães, Diego V. Wilke, Daniel P. Bezerra, Bruno C. Cavalcanti, Rodrigo Rotta, Dênis P. de Lima, Adilson Beatriz, Manoel O. Moraes, Jairo Diniz-Filho, Claudia Pessoa, (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G2/M arrest, and triggers apoptosis in human leukemia HL-60 cells Toxicology and Applied Pharmacology. ,vol. 272, pp. 117- 126 ,(2013) , 10.1016/J.TAAP.2013.06.001