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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Bibliographic Details
Published in:PeerJ (San Francisco, CA) CA), 2016-03, Vol.4, p.e1588-e1588
Main Authors: Samie, Nima, Muniandy, Sekaran, Kanthimathi, M S, Haerian, Batoul Sadat
Format: Article
Language:English
Subjects:
Apoptosis
Cancer therapies
Caspase
Caspase-3
Caspase-8
Cell cycle
Chemotherapy
Chromatography
Cytochrome c
Cytoskeletal rearrangement
Cytotoxicity
Deoxyribonucleic acid
DNA
Flow cytometry
G1 phase
Glutathione reductase
Hepatocytes
Leukemia
Liver cancer
Medical research
Medicine
Membrane potential
Metastasis
Mitochondria
NF-κB protein
Oncology
Pharmaceutical sciences
Pharmacology
Piperazine
Signal transduction
Toxicology
Tumor cell lines
Tumors
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Summary: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.
ISSN:2167-8359
2167-8359
DOI:10.7717/peerj.1588