Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents
In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R = iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/45530/1/ZINC.pdf |
| _version_ | 1825929578781081600 |
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| author | Cheah, Yoke Kqueen Md. Akim, Abdah Tiekink, Edward R. T. Yee, Seng Tan Abdul Halim, Siti Nadiah Seng, Hoi Ling Ooi, Kah Kooi Kok, Pian Ang |
| author_facet | Cheah, Yoke Kqueen Md. Akim, Abdah Tiekink, Edward R. T. Yee, Seng Tan Abdul Halim, Siti Nadiah Seng, Hoi Ling Ooi, Kah Kooi Kok, Pian Ang |
| author_sort | Cheah, Yoke Kqueen |
| collection | UPM |
| description | In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R = iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as monohydrates. All compounds were broadly cytotoxic, specifically against human cancer cell lines compared with normal cells, with greater potency than cisplatin. Notably, some selectivity were indicated with 2 being the most potent against human ovarian carcinoma cells (cisA2780), and 4 being more cytotoxic toward multidrug resistant human breast carcinoma cells (MCF-7R), human colon adenocarcinoma cells (HT-29), and human lung adenocarcinoma epithelial cells (A549). Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis in HT-29 cells is demonstrated via both extrinsic and intrinsic pathways. Compounds 2–4 activate the p53 gene while 1 activates both p53 and p73. Cell cycle arrest at the S and G2/M phases correlates with inhibition of HT-29 cell growth. Cell invasion is also inhibited by 1–4 which is correlated with down-regulation of NF-κB. |
| first_indexed | 2024-03-06T08:58:47Z |
| format | Article |
| id | upm.eprints-45530 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T08:58:47Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | upm.eprints-455302021-01-26T19:19:53Z http://psasir.upm.edu.my/id/eprint/45530/ Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents Cheah, Yoke Kqueen Md. Akim, Abdah Tiekink, Edward R. T. Yee, Seng Tan Abdul Halim, Siti Nadiah Seng, Hoi Ling Ooi, Kah Kooi Kok, Pian Ang In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R = iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as monohydrates. All compounds were broadly cytotoxic, specifically against human cancer cell lines compared with normal cells, with greater potency than cisplatin. Notably, some selectivity were indicated with 2 being the most potent against human ovarian carcinoma cells (cisA2780), and 4 being more cytotoxic toward multidrug resistant human breast carcinoma cells (MCF-7R), human colon adenocarcinoma cells (HT-29), and human lung adenocarcinoma epithelial cells (A549). Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis in HT-29 cells is demonstrated via both extrinsic and intrinsic pathways. Compounds 2–4 activate the p53 gene while 1 activates both p53 and p73. Cell cycle arrest at the S and G2/M phases correlates with inhibition of HT-29 cell growth. Cell invasion is also inhibited by 1–4 which is correlated with down-regulation of NF-κB. Elsevier 2015 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/45530/1/ZINC.pdf Cheah, Yoke Kqueen and Md. Akim, Abdah and Tiekink, Edward R. T. and Yee, Seng Tan and Abdul Halim, Siti Nadiah and Seng, Hoi Ling and Ooi, Kah Kooi and Kok, Pian Ang (2015) Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents. Journal of Inorganic Biochemistry, 150 (9). pp. 48-62. ISSN 0162-0134; ESSN: 1873-3344 https://www.sciencedirect.com/science/article/pii/S0162013415300143 10.1016/j.jinorgbio.2015.06.009 |
| spellingShingle | Cheah, Yoke Kqueen Md. Akim, Abdah Tiekink, Edward R. T. Yee, Seng Tan Abdul Halim, Siti Nadiah Seng, Hoi Ling Ooi, Kah Kooi Kok, Pian Ang Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents |
| title | Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents |
| title_full | Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents |
| title_fullStr | Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents |
| title_full_unstemmed | Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents |
| title_short | Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents |
| title_sort | molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents |
| url | http://psasir.upm.edu.my/id/eprint/45530/1/ZINC.pdf |
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