Affiliations 

  • 1 Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 2 Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
  • 3 Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia. Electronic address: ykcheah@medic.upm.edu.my
  • 4 Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia; Department of Biological Sciences, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia
  • 5 Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: Edward.Tiekink@um.edu.my
J. Inorg. Biochem., 2015 Sep;150:48-62.
PMID: 26086852 DOI: 10.1016/j.jinorgbio.2015.06.009

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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