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Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells

The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liv...

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Autores principales: Samie, Nima, Muniandy, Sekaran, Kanthimathi, MS, Haerian, Batoul Sadat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806608/
https://www.ncbi.nlm.nih.gov/pubmed/27019772
http://dx.doi.org/10.7717/peerj.1588
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author Samie, Nima
Muniandy, Sekaran
Kanthimathi, MS
Haerian, Batoul Sadat
author_facet Samie, Nima
Muniandy, Sekaran
Kanthimathi, MS
Haerian, Batoul Sadat
author_sort Samie, Nima
collection PubMed
description The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liver cancer cells with an IC50 value of 6.98 ± 0.11 µM and 7.76 ± 0.45 µM against SNU-475 and SNU-423 respectively after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of this study suggest that PCC is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.
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spelling pubmed-48066082016-03-25 Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells Samie, Nima Muniandy, Sekaran Kanthimathi, MS Haerian, Batoul Sadat PeerJ Toxicology The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liver cancer cells with an IC50 value of 6.98 ± 0.11 µM and 7.76 ± 0.45 µM against SNU-475 and SNU-423 respectively after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of this study suggest that PCC is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PeerJ Inc. 2016-03-17 /pmc/articles/PMC4806608/ /pubmed/27019772 http://dx.doi.org/10.7717/peerj.1588 Text en ©2016 Samie et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Toxicology
Samie, Nima
Muniandy, Sekaran
Kanthimathi, MS
Haerian, Batoul Sadat
Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells
title Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells
title_full Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells
title_fullStr Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells
title_full_unstemmed Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells
title_short Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells
title_sort mechanism of action of novel piperazine containing a toxicant against human liver cancer cells
topic Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806608/
https://www.ncbi.nlm.nih.gov/pubmed/27019772
http://dx.doi.org/10.7717/peerj.1588
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