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

Nima Samie; Sekaran Muniandy; M S Kanthimathi; Batoul Sadat Haerian

doi:10.7717/peerj.1588

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

PeerJ. 2016 Mar 17:4:e1588. doi: 10.7717/peerj.1588. eCollection 2016.

Authors

Nima Samie¹, Sekaran Muniandy², M S Kanthimathi³, Batoul Sadat Haerian¹

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
² Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
³ Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; University of Malaya Centre for Proteomics Research, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Abstract

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.

Keywords: Apoptosis; Cytoskeletal rearrangement; Liver cancer; Piperazine.

Publication types

Retracted Publication

Grants and funding

This study was funded by the University of Malaya and Ministry of Higher Education (HIR Grant H-20001-00-E00046) and Postgraduate Research Grant (PG021-2014B). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.