Limits...
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

PCC arrests the cell cycle in the S/M phase.Cells were incubated with DMSO (negative control) and PCC (6.25 μg/ml) for 24 h, followed by collection and staining with BrdU and Phopho-Histone H3. Treatment with PCC revealed no significant changes in the BrdU and Phosho-Histone H3 fluorescence intensity which suggests that the cells have not been arrested at S/M phase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4829832&req=5

f1: PCC arrests the cell cycle in the S/M phase.Cells were incubated with DMSO (negative control) and PCC (6.25 μg/ml) for 24 h, followed by collection and staining with BrdU and Phopho-Histone H3. Treatment with PCC revealed no significant changes in the BrdU and Phosho-Histone H3 fluorescence intensity which suggests that the cells have not been arrested at S/M phase.

Mentions: Development of cancer is due to dysfunction in the regulation of the cell cycle that appears in over-proliferation of cells, although cancer progression can be strongly limited by conquest of the cell cycle. Hence, the effect of 6.25 μg/ml PCC on cell cycle arrest was investigated. The BrdU and phospho-histone H3 staining of SNU-475 and SNU-423 cells treated with PCC showed that cell cycle arrest at the S/M phases did not occur (Fig. 1). However, cellular arrest in the G1 phase was detected by using flow cytometry (Fig. 2).


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)

PCC arrests the cell cycle in the S/M phase.Cells were incubated with DMSO (negative control) and PCC (6.25 μg/ml) for 24 h, followed by collection and staining with BrdU and Phopho-Histone H3. Treatment with PCC revealed no significant changes in the BrdU and Phosho-Histone H3 fluorescence intensity which suggests that the cells have not been arrested at S/M phase.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: PCC arrests the cell cycle in the S/M phase.Cells were incubated with DMSO (negative control) and PCC (6.25 μg/ml) for 24 h, followed by collection and staining with BrdU and Phopho-Histone H3. Treatment with PCC revealed no significant changes in the BrdU and Phosho-Histone H3 fluorescence intensity which suggests that the cells have not been arrested at S/M phase.
Mentions: Development of cancer is due to dysfunction in the regulation of the cell cycle that appears in over-proliferation of cells, although cancer progression can be strongly limited by conquest of the cell cycle. Hence, the effect of 6.25 μg/ml PCC on cell cycle arrest was investigated. The BrdU and phospho-histone H3 staining of SNU-475 and SNU-423 cells treated with PCC showed that cell cycle arrest at the S/M phases did not occur (Fig. 1). However, cellular arrest in the G1 phase was detected by using flow cytometry (Fig. 2).

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