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Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties

The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used...

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Autores principales: Samie, Nima, Muniandy, Sekaran, Kanthimathi, M. S., Haerian, Batoul Sadat, Raja Azudin, Raja Elina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829832/
https://www.ncbi.nlm.nih.gov/pubmed/27072064
http://dx.doi.org/10.1038/srep24172
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author Samie, Nima
Muniandy, Sekaran
Kanthimathi, M. S.
Haerian, Batoul Sadat
Raja Azudin, Raja Elina
author_facet Samie, Nima
Muniandy, Sekaran
Kanthimathi, M. S.
Haerian, Batoul Sadat
Raja Azudin, Raja Elina
author_sort Samie, Nima
collection PubMed
description The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC(50) of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC(50) value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml 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-ƙB 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. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.
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spelling pubmed-48298322016-04-19 Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties Samie, Nima Muniandy, Sekaran Kanthimathi, M. S. Haerian, Batoul Sadat Raja Azudin, Raja Elina Sci Rep Article The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC(50) of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC(50) value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml 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-ƙB 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. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. Nature Publishing Group 2016-04-13 /pmc/articles/PMC4829832/ /pubmed/27072064 http://dx.doi.org/10.1038/srep24172 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Samie, Nima
Muniandy, Sekaran
Kanthimathi, M. S.
Haerian, Batoul Sadat
Raja Azudin, Raja Elina
Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
title Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
title_full Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
title_fullStr Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
title_full_unstemmed Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
title_short Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
title_sort novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829832/
https://www.ncbi.nlm.nih.gov/pubmed/27072064
http://dx.doi.org/10.1038/srep24172
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