Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells

Scientific Reports
Larissa M BomfimDaniel P Bezerra

Abstract

Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)2(PPh3)2] (1) and [Ru(6m2tu)2(dppb)] (2) (where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane; and 6m2tu = 6-methyl-2-thiouracil) are potent cytotoxic agents and able to bind DNA. The aim of this study was to evaluate in vitro cellular underlying mechanism and in vivo effectiveness of these ruthenium(II) complexes in human acute promyelocytic leukemia HL-60 cells. Both complexes displayed potent and selective cytotoxicity in myeloid leukemia cell lines, and were detected into HL-60 cells. Reduction of the cell proliferation and augmented phosphatidylserine externalization, caspase-3, -8 and -9 activation and loss of mitochondrial transmembrane potential were observed in HL-60 cells treated with both complexes. Cotreatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced Ru(II) complexes-induced apoptosis. In addition, both metal complexes induced phosphorylation of histone H2AX (S139), JNK2 (T183/Y185) and p38α (T180/Y182), and cotreatment with JNK/SAPK and p38 MAPK inhibitors reduced complexes-induced apoptosis, indicating DNA double-strand break and activation of caspase-mediated apoptosis through JNK/p38 pathways. Complex 1 also reduce...Continue Reading

References

Aug 1, 1996·Journal of Microscopy·R G KirkP Lee
Sep 20, 2000·The Journal of Biological Chemistry·X WangN J Holbrook
Feb 12, 2009·Anti-cancer Drugs·Frederike LentzUNKNOWN Central European Society for Anticancer Drug Research-EWIV
Feb 19, 2013·Mutation Research·Vanessa ValdiglesiasStefano Bonassi
Feb 19, 2015·Archives of Toxicology·Eun Kyung Kim, Eui-Ju Choi
Apr 18, 2015·Blood Cancer Journal·C C CoombsM S Tallman
Dec 15, 2015·Blood·Hervé Dombret, Claude Gardin
Sep 14, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Dongdong SunWeiyun Wang
Feb 1, 2017·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Olga MazurykMałgorzata Brindell
Dec 21, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jincan ChenLanmei Chen
Jan 13, 2018·Scientific Reports·Valdenizia Rodrigues SilvaDaniel Pereira Bezerra
Feb 16, 2018·Journal of Medicinal Chemistry·Sreekanth ThotaEliezer J Barreiro
Jun 1, 2018·International Journal of Molecular Sciences·Maiara de Souza OliveiraDaniel Pereira Bezerra
Nov 18, 2018·Journal of Ethnopharmacology·Ana Carolina B da C RodriguesDaniel P Bezerra

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Methods Mentioned

BETA
gene knockout
X-ray
light microscopy
flow cytometry
Protein Assay
xenograft
light scattering
light
ELISA
xenografts

Software Mentioned

GraphPad Prism
Flowjo
Image
Pro

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