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Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2015 Sep; Vol. 150, pp. 48-62. Date of Electronic Publication: 2015 Jun 09. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents toxicity
Apoptosis drug effects
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Coordination Complexes chemical synthesis
Coordination Complexes chemistry
Coordination Complexes toxicity
Genes, p53
Humans
NF-kappa B genetics
Neoplasm Invasiveness
RNA, Messenger genetics
Rats
Thiocarbamates chemical synthesis
Thiocarbamates chemistry
Thiocarbamates toxicity
Topoisomerase I Inhibitors chemical synthesis
Topoisomerase I Inhibitors chemistry
Topoisomerase I Inhibitors toxicity
Antineoplastic Agents pharmacology
Coordination Complexes pharmacology
Thiocarbamates pharmacology
Topoisomerase I Inhibitors pharmacology
Zinc chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 150
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26086852
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2015.06.009