title: Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties.
abstract: 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 IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Nima
authors.initials: N
authors.lastname: Samie
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sekaran
authors.initials: S
authors.lastname: Muniandy
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.|University of Malaya Centre for Proteomics Research, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: M S
authors.initials: MS
authors.lastname: Kanthimathi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Batoul Sadat
authors.initials: BS
authors.lastname: Haerian
authors.affiliation: Drug and research unit, Department of Pathology, Hospital Kuala Lumpur (HKL), 50586 Kuala Lumpur, Malaysia.
authors.forename: Raja Elina Raja
authors.initials: RE
authors.lastname: Azudin