Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC 6H 4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination
| Autor: | Yoke Kqueen Cheah, Siti Nadiah Abdul Halim, Chien Ing Yeo, Kok-Pian Ang, Kah Kooi Ooi, Edward R. T. Tiekink, Hoi-Ling Seng, Abdah Md Akim |
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| Rok vydání: | 2014 |
| Předmět: |
Cell cycle checkpoint
Cell Survival Phosphines Cell Antineoplastic Agents Apoptosis Biochemistry Inorganic Chemistry Structure-Activity Relationship Ubiquitin medicine Cytotoxic T cell Humans Neoplasm Invasiveness Sulfhydryl Compounds Caspase Cell Proliferation biology Molecular Structure Chemistry Spheroid NF-kappa B Ubiquitination Cell Cycle Checkpoints Cell biology medicine.anatomical_structure Colonic Neoplasms biology.protein DNA fragmentation HT29 Cells Organogold Compounds Signal Transduction |
| Zdroj: | Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 20(5) |
| ISSN: | 1432-1327 |
| Popis: | The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P–Au–S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1–3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1–3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1–3 and these are able to inhibit cell invasion and to suppress the activity of TrxR. |
| Databáze: | OpenAIRE |
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