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

International Journal of Molecular Sciences
Maiara de Souza OliveiraDaniel P Bezerra

Abstract

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

References

Sep 15, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Daniel Pereira BezerraLetícia Veras Costa-Lotufo
Feb 12, 2009·Anti-cancer Drugs·Frederike LentzUNKNOWN Central European Society for Anticancer Drug Research-EWIV
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Sep 4, 2017·Journal of Inorganic Biochemistry·Katia M OliveiraAlzir A Batista
Jan 13, 2018·Scientific Reports·Valdenizia Rodrigues SilvaDaniel Pereira Bezerra
Jan 25, 2018·Cell Death and Differentiation·Lorenzo GalluzziGuido Kroemer
Jan 25, 2018·Oxidative Medicine and Cellular Longevity·Luciano de Souza SantosDaniel Pereira Bezerra
Feb 24, 2018·Scientific Reports·Andrana Karla CalgarottoSara Teresinha Olalla Saad

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
gene knockout

Software Mentioned

Flowjo
GraphPad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.