Tan, Yee Seng and Ooi, Kah Kooi and Ang, Kok Pian and Akim, Abdah Md and Cheah, Yoke Kqueen and Halim, Siti Nadiah Abdul and Seng, Hoi Ling and Tiekink, Edward R.T. (2015) Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents. Journal of Inorganic Biochemistry, 150. pp. 48-62. ISSN 0162-0134, DOI https://doi.org/10.1016/j.jinorgbio.2015.06.009.
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Funders: | High Impact Research MoE Grants UM.C/625/1/HIR/MoE/SC/03 and UM.C/625/1/HIR/MoE/SC/12 from the Ministry of Higher Education, Malaysia |
| Uncontrolled Keywords: | Zinc; Dithiocarbamate; Cell selectivity; Apoptosis; Cell cycle; Topoisomerase I |
| Subjects: | Q Science > Q Science (General) Q Science > QD Chemistry |
| Divisions: | Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 05 Oct 2018 03:23 |
| Last Modified: | 23 Dec 2019 04:26 |
| URI: | http://eprints.um.edu.my/id/eprint/19602 |
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