A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway

The compound with R = CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R = CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activitie...

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Main Authors: Abang Ishak, Dayang Hazwani, Ooi, Kah Kooi, Ang, Kok Pian, Md. Akim, Abdah, Cheah, Yoke Kqueen, Nordin, Norshariza, Abdul Halim, Siti Nadiah, Seng, Hoi Ling, Tiekink, Edward R. T.
Format: Article
Language:English
Published: Elsevier 2014
Online Access:http://psasir.upm.edu.my/id/eprint/36121/
http://psasir.upm.edu.my/id/eprint/36121/1/A%20bismuth%20diethyldithiocarbamate%20compound%20promotes%20apoptosis%20in%20HepG2%20carcinoma.pdf
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author Abang Ishak, Dayang Hazwani
Ooi, Kah Kooi
Ang, Kok Pian
Md. Akim, Abdah
Cheah, Yoke Kqueen
Nordin, Norshariza
Abdul Halim, Siti Nadiah
Seng, Hoi Ling
Tiekink, Edward R. T.
author_facet Abang Ishak, Dayang Hazwani
Ooi, Kah Kooi
Ang, Kok Pian
Md. Akim, Abdah
Cheah, Yoke Kqueen
Nordin, Norshariza
Abdul Halim, Siti Nadiah
Seng, Hoi Ling
Tiekink, Edward R. T.
author_sort Abang Ishak, Dayang Hazwani
building UPM Institutional Repository
collection Online Access
description The compound with R = CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R = CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor-dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-κB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes.
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spelling upm-361212015-08-25T07:26:08Z http://psasir.upm.edu.my/id/eprint/36121/ A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway Abang Ishak, Dayang Hazwani Ooi, Kah Kooi Ang, Kok Pian Md. Akim, Abdah Cheah, Yoke Kqueen Nordin, Norshariza Abdul Halim, Siti Nadiah Seng, Hoi Ling Tiekink, Edward R. T. The compound with R = CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R = CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor-dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-κB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes. Elsevier 2014-01 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/36121/1/A%20bismuth%20diethyldithiocarbamate%20compound%20promotes%20apoptosis%20in%20HepG2%20carcinoma.pdf Abang Ishak, Dayang Hazwani and Ooi, Kah Kooi and Ang, Kok Pian and Md. Akim, Abdah and Cheah, Yoke Kqueen and Nordin, Norshariza and Abdul Halim, Siti Nadiah and Seng, Hoi Ling and Tiekink, Edward R. T. (2014) A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway. Journal of Inorganic Biochemistry, 130. pp. 38-51. ISSN 0162-0134; ESSN: 1873-3344 10.1016/j.jinorgbio.2013.09.018
spellingShingle Abang Ishak, Dayang Hazwani
Ooi, Kah Kooi
Ang, Kok Pian
Md. Akim, Abdah
Cheah, Yoke Kqueen
Nordin, Norshariza
Abdul Halim, Siti Nadiah
Seng, Hoi Ling
Tiekink, Edward R. T.
A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
title A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
title_full A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
title_fullStr A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
title_full_unstemmed A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
title_short A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
title_sort bismuth diethyldithiocarbamate compound promotes apoptosis in hepg2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the nf-κb activation pathway
url http://psasir.upm.edu.my/id/eprint/36121/
http://psasir.upm.edu.my/id/eprint/36121/
http://psasir.upm.edu.my/id/eprint/36121/1/A%20bismuth%20diethyldithiocarbamate%20compound%20promotes%20apoptosis%20in%20HepG2%20carcinoma.pdf