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

Samie N, Muniandy S, Kanthimathi MS, Haerian BS, Azudin RE - Sci Rep (2016)

Bottom Line: 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.Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9.Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

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.

No MeSH data available.


Related in: MedlinePlus

Cytotoxic evaluation of PCC using lactate dehydrogenase (LDH) assay.Bar charts show that PCC was significantly able to elevate the release of LDH at the concentration of 6.25 μg/ml. All data are expressed as the means ± standard error of triplicate measurements. *P < 0.05 compared with the no-treatment group.
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f9: Cytotoxic evaluation of PCC using lactate dehydrogenase (LDH) assay.Bar charts show that PCC was significantly able to elevate the release of LDH at the concentration of 6.25 μg/ml. All data are expressed as the means ± standard error of triplicate measurements. *P < 0.05 compared with the no-treatment group.

Mentions: Lactate dehydrogenase (LDH) is a cytosolic enzyme and serves as a biomarker for cellular cytotoxicity, loss of membrane integrity and cytolysis. PCC significantly induced release of this enzyme at a concentration of 6.25 μg/ml after 24 h showing the potential cytotoxic effect of PCC on cancer cell lines (Fig. 9).


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

Samie N, Muniandy S, Kanthimathi MS, Haerian BS, Azudin RE - Sci Rep (2016)

Cytotoxic evaluation of PCC using lactate dehydrogenase (LDH) assay.Bar charts show that PCC was significantly able to elevate the release of LDH at the concentration of 6.25 μg/ml. All data are expressed as the means ± standard error of triplicate measurements. *P < 0.05 compared with the no-treatment group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829832&req=5

f9: Cytotoxic evaluation of PCC using lactate dehydrogenase (LDH) assay.Bar charts show that PCC was significantly able to elevate the release of LDH at the concentration of 6.25 μg/ml. All data are expressed as the means ± standard error of triplicate measurements. *P < 0.05 compared with the no-treatment group.
Mentions: Lactate dehydrogenase (LDH) is a cytosolic enzyme and serves as a biomarker for cellular cytotoxicity, loss of membrane integrity and cytolysis. PCC significantly induced release of this enzyme at a concentration of 6.25 μg/ml after 24 h showing the potential cytotoxic effect of PCC on cancer cell lines (Fig. 9).

Bottom Line: 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.Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9.Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

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.

No MeSH data available.


Related in: MedlinePlus