Novel Organotin(IV) Dithiocarbamate: Cytotoxicity Evaluation and the Toxicity Mechanism in Human Leukemia Cell Lines

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Abstract

The organotin(IV) dithiocarbamate derivatives have good cytotoxicity potentials. However, their mechanisms of action against cancer cells and their effects towards normal human cells are still unclear. In this study, four novel organotin(IV) N-butyl-Nphenyldithiocarbamate compounds with the formula RSn[S2CNC4H9(C6H5)]n (for n = 2, R = C4H9, C6H5; for n = 3, R = C6H5) were synthesized to evaluate their cytotoxicity potential and to determine the mechanism of action of the most potential compound in human leukemia cell lines. The Jurkat E6.1, HL-60 and K562 cell lines were treated with all compounds for 24 h prior to assessment via 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazholium bromide (MTT) assay. The genotoxicity of the compound was assessed via alkaline comet assay. Meanwhile, the dihidroethidium, N-acetyl-L-cysteine and tetramethylrhodamine ethyl ester assays were conducted to determine the role of the intracellular oxidative stress and the loss of mitochondrial membrane potential (Δψm) respectively. The apoptotic pathway involved was determined via caspase activation assay. The percentage of untreated cells along with compounds treated cells was calculated using one-way ANOVA (analysis of variance). All compounds exhibited a strong cytotoxicity in the Jurkat E6.1, HL-60 and K562 cell lines with IC50 values in the ranges 0.40-1.30 μM, 0.23-6.90 μM, and 1.85-7.00 μM respectively. Compound 4 (triphenyltin(IV) N-butyl-Nphenyldithiocarbamate) demonstrated the induction of reactive oxygen species (ROS) excessively in K562 cells, probably causing oxidative damage to DNA. Subsequently, decreases in Δψm and the activation of caspase 9 suggested that the cells died via the intrinsic pathway of apoptosis. In conclusion, the organotin(IV) N-butyl-N-phenyldithiocarbamate compounds demonstrated a good toxicity against the human leukemia cell lines tested. The generation of ROS was suggested as an important factor in inducing DNA damage and disrupting the normal mitochondrial function, consequently causing apoptosis.

Original languageEnglish
Pages (from-to)5-19
Number of pages15
JournalResearch Journal of Chemistry and Environment
Volume20
Issue number6
Publication statusPublished - 2016

Fingerprint

Cytotoxicity
leukemia
Toxicity
cytotoxicity
Leukemia
Cells
cell lines
assay
K562 Cells
toxicity
Cell Line
apoptosis
Assays
HL-60 Cells
assays
DNA Damage
cells
reactive oxygen species
Reactive Oxygen Species
mechanism of action

Keywords

  • Apoptosis
  • Cytotoxicity
  • Dithiocarbamate
  • Leukemia
  • Tin
  • Toxicity mechanism

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Chemical Engineering(all)
  • Renewable Energy, Sustainability and the Environment
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)
  • Earth and Planetary Sciences(all)

Cite this

@article{3eadc0c7763b4543b65884c2a8a17646,
title = "Novel Organotin(IV) Dithiocarbamate: Cytotoxicity Evaluation and the Toxicity Mechanism in Human Leukemia Cell Lines",
abstract = "The organotin(IV) dithiocarbamate derivatives have good cytotoxicity potentials. However, their mechanisms of action against cancer cells and their effects towards normal human cells are still unclear. In this study, four novel organotin(IV) N-butyl-Nphenyldithiocarbamate compounds with the formula RSn[S2CNC4H9(C6H5)]n (for n = 2, R = C4H9, C6H5; for n = 3, R = C6H5) were synthesized to evaluate their cytotoxicity potential and to determine the mechanism of action of the most potential compound in human leukemia cell lines. The Jurkat E6.1, HL-60 and K562 cell lines were treated with all compounds for 24 h prior to assessment via 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazholium bromide (MTT) assay. The genotoxicity of the compound was assessed via alkaline comet assay. Meanwhile, the dihidroethidium, N-acetyl-L-cysteine and tetramethylrhodamine ethyl ester assays were conducted to determine the role of the intracellular oxidative stress and the loss of mitochondrial membrane potential (Δψm) respectively. The apoptotic pathway involved was determined via caspase activation assay. The percentage of untreated cells along with compounds treated cells was calculated using one-way ANOVA (analysis of variance). All compounds exhibited a strong cytotoxicity in the Jurkat E6.1, HL-60 and K562 cell lines with IC50 values in the ranges 0.40-1.30 μM, 0.23-6.90 μM, and 1.85-7.00 μM respectively. Compound 4 (triphenyltin(IV) N-butyl-Nphenyldithiocarbamate) demonstrated the induction of reactive oxygen species (ROS) excessively in K562 cells, probably causing oxidative damage to DNA. Subsequently, decreases in Δψm and the activation of caspase 9 suggested that the cells died via the intrinsic pathway of apoptosis. In conclusion, the organotin(IV) N-butyl-N-phenyldithiocarbamate compounds demonstrated a good toxicity against the human leukemia cell lines tested. The generation of ROS was suggested as an important factor in inducing DNA damage and disrupting the normal mitochondrial function, consequently causing apoptosis.",
keywords = "Apoptosis, Cytotoxicity, Dithiocarbamate, Leukemia, Tin, Toxicity mechanism",
author = "{Nurul Farahana}, Kamaludin and Normah Awang and Baba Ibrahim and Asmah Hamid and {Kok Meng}, Chan",
year = "2016",
language = "English",
volume = "20",
pages = "5--19",
journal = "Research Journal of Chemistry and Environment",
issn = "0972-0626",
publisher = "International Congress of Chemistry and Environment",
number = "6",

}

TY - JOUR

T1 - Novel Organotin(IV) Dithiocarbamate

T2 - Cytotoxicity Evaluation and the Toxicity Mechanism in Human Leukemia Cell Lines

AU - Nurul Farahana, Kamaludin

AU - Awang, Normah

AU - Ibrahim, Baba

AU - Hamid, Asmah

AU - Kok Meng, Chan

PY - 2016

Y1 - 2016

N2 - The organotin(IV) dithiocarbamate derivatives have good cytotoxicity potentials. However, their mechanisms of action against cancer cells and their effects towards normal human cells are still unclear. In this study, four novel organotin(IV) N-butyl-Nphenyldithiocarbamate compounds with the formula RSn[S2CNC4H9(C6H5)]n (for n = 2, R = C4H9, C6H5; for n = 3, R = C6H5) were synthesized to evaluate their cytotoxicity potential and to determine the mechanism of action of the most potential compound in human leukemia cell lines. The Jurkat E6.1, HL-60 and K562 cell lines were treated with all compounds for 24 h prior to assessment via 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazholium bromide (MTT) assay. The genotoxicity of the compound was assessed via alkaline comet assay. Meanwhile, the dihidroethidium, N-acetyl-L-cysteine and tetramethylrhodamine ethyl ester assays were conducted to determine the role of the intracellular oxidative stress and the loss of mitochondrial membrane potential (Δψm) respectively. The apoptotic pathway involved was determined via caspase activation assay. The percentage of untreated cells along with compounds treated cells was calculated using one-way ANOVA (analysis of variance). All compounds exhibited a strong cytotoxicity in the Jurkat E6.1, HL-60 and K562 cell lines with IC50 values in the ranges 0.40-1.30 μM, 0.23-6.90 μM, and 1.85-7.00 μM respectively. Compound 4 (triphenyltin(IV) N-butyl-Nphenyldithiocarbamate) demonstrated the induction of reactive oxygen species (ROS) excessively in K562 cells, probably causing oxidative damage to DNA. Subsequently, decreases in Δψm and the activation of caspase 9 suggested that the cells died via the intrinsic pathway of apoptosis. In conclusion, the organotin(IV) N-butyl-N-phenyldithiocarbamate compounds demonstrated a good toxicity against the human leukemia cell lines tested. The generation of ROS was suggested as an important factor in inducing DNA damage and disrupting the normal mitochondrial function, consequently causing apoptosis.

AB - The organotin(IV) dithiocarbamate derivatives have good cytotoxicity potentials. However, their mechanisms of action against cancer cells and their effects towards normal human cells are still unclear. In this study, four novel organotin(IV) N-butyl-Nphenyldithiocarbamate compounds with the formula RSn[S2CNC4H9(C6H5)]n (for n = 2, R = C4H9, C6H5; for n = 3, R = C6H5) were synthesized to evaluate their cytotoxicity potential and to determine the mechanism of action of the most potential compound in human leukemia cell lines. The Jurkat E6.1, HL-60 and K562 cell lines were treated with all compounds for 24 h prior to assessment via 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazholium bromide (MTT) assay. The genotoxicity of the compound was assessed via alkaline comet assay. Meanwhile, the dihidroethidium, N-acetyl-L-cysteine and tetramethylrhodamine ethyl ester assays were conducted to determine the role of the intracellular oxidative stress and the loss of mitochondrial membrane potential (Δψm) respectively. The apoptotic pathway involved was determined via caspase activation assay. The percentage of untreated cells along with compounds treated cells was calculated using one-way ANOVA (analysis of variance). All compounds exhibited a strong cytotoxicity in the Jurkat E6.1, HL-60 and K562 cell lines with IC50 values in the ranges 0.40-1.30 μM, 0.23-6.90 μM, and 1.85-7.00 μM respectively. Compound 4 (triphenyltin(IV) N-butyl-Nphenyldithiocarbamate) demonstrated the induction of reactive oxygen species (ROS) excessively in K562 cells, probably causing oxidative damage to DNA. Subsequently, decreases in Δψm and the activation of caspase 9 suggested that the cells died via the intrinsic pathway of apoptosis. In conclusion, the organotin(IV) N-butyl-N-phenyldithiocarbamate compounds demonstrated a good toxicity against the human leukemia cell lines tested. The generation of ROS was suggested as an important factor in inducing DNA damage and disrupting the normal mitochondrial function, consequently causing apoptosis.

KW - Apoptosis

KW - Cytotoxicity

KW - Dithiocarbamate

KW - Leukemia

KW - Tin

KW - Toxicity mechanism

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JF - Research Journal of Chemistry and Environment

SN - 0972-0626

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