Cytotoxic behavior of binuclear silver N-heterocyclic carbenes in HCT 116 cells and influence of substitution on cytotoxicity

Cytotoxic behavior of binuclear silver N-heterocyclic carbenes in HCT 116 cells and influence of... Ag (I)-N-heterocyclic carbene (Ag–NHC) complexes (S1–S6) were synthesized from di-cationic ionic liquids (DCILs-1–6) and characterized by NMR, FT-IR, and EI-MS studies, and evaluated for cytotoxicity against human colorectal carcinoma cell line (HCT-116) using methylthiazolyldiphenyl-tetrazolium bromide assay. The DCILs displayed good patterns of cytotoxicity which was improved greatly upon metallation and were found to be in a direct correlation with the increase in the alkyl chain that correlates with lipophilicity. Amongst the Ag–NHCs studied, S1, S5, and S6 have shown 85.95, 99.01 and 99.70% growth inhibition at the concentrations of 120, 120 and 60 µM, respectively. In order to depict the putative mechanism adopted by S6, HCT-116 cells were treated with S6 and stained using acridine orange/ethidium bromide (AO/EtBr), and the results displayed a significant induction of apoptosis in HCT-116 cells as evident from the green-orange fluorescence. Furthermore, DAPI staining confirmed that the S6-treated HCT-116 cells underwent chromatin condensation and DNA fragmentation. Since mitochondria play a prominent role in apoptosis, we further examined the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) formation. Interestingly, the S6-treated HCT-116 cells demonstrated a higher ROS and depolarization of MMP, which suggests that S6 can induce mitochondria-mediated intrinsic apoptosis in cancer cells. Besides these consequences, HCT-116 cells also exhibited a lower level of oxidant defensive protein catalase. Taken altogether, the current study suggests that Ag–NHCs can reduce anti-oxidative protein catalase following an increase in ROS level, thereby triggering apoptosis in cancer cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Research on Chemical Intermediates Springer Journals

Cytotoxic behavior of binuclear silver N-heterocyclic carbenes in HCT 116 cells and influence of substitution on cytotoxicity

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Publisher
Springer Netherlands
Copyright
Copyright © 2017 by Springer Science+Business Media Dordrecht
Subject
Chemistry; Catalysis; Physical Chemistry; Inorganic Chemistry
ISSN
0922-6168
eISSN
1568-5675
D.O.I.
10.1007/s11164-017-2916-5
Publisher site
See Article on Publisher Site

Abstract

Ag (I)-N-heterocyclic carbene (Ag–NHC) complexes (S1–S6) were synthesized from di-cationic ionic liquids (DCILs-1–6) and characterized by NMR, FT-IR, and EI-MS studies, and evaluated for cytotoxicity against human colorectal carcinoma cell line (HCT-116) using methylthiazolyldiphenyl-tetrazolium bromide assay. The DCILs displayed good patterns of cytotoxicity which was improved greatly upon metallation and were found to be in a direct correlation with the increase in the alkyl chain that correlates with lipophilicity. Amongst the Ag–NHCs studied, S1, S5, and S6 have shown 85.95, 99.01 and 99.70% growth inhibition at the concentrations of 120, 120 and 60 µM, respectively. In order to depict the putative mechanism adopted by S6, HCT-116 cells were treated with S6 and stained using acridine orange/ethidium bromide (AO/EtBr), and the results displayed a significant induction of apoptosis in HCT-116 cells as evident from the green-orange fluorescence. Furthermore, DAPI staining confirmed that the S6-treated HCT-116 cells underwent chromatin condensation and DNA fragmentation. Since mitochondria play a prominent role in apoptosis, we further examined the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) formation. Interestingly, the S6-treated HCT-116 cells demonstrated a higher ROS and depolarization of MMP, which suggests that S6 can induce mitochondria-mediated intrinsic apoptosis in cancer cells. Besides these consequences, HCT-116 cells also exhibited a lower level of oxidant defensive protein catalase. Taken altogether, the current study suggests that Ag–NHCs can reduce anti-oxidative protein catalase following an increase in ROS level, thereby triggering apoptosis in cancer cells.

Journal

Research on Chemical IntermediatesSpringer Journals

Published: Feb 27, 2017

References

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