caa a22 4500 605507759 CHVBK 20210128100633.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00775-015-1271-5 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1271-5 Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC6H4Me-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 [Elektronische Daten] [Kah Ooi, Chien Yeo, Kok-Pian Ang, Abdah Akim, Yoke-Kqueen Cheah, Siti Halim, Hoi-Ling Seng, Edward Tiekink] 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±0.3μM 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. Graphical abstract: 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. SBIC, 2015 Gold(I) compounds nationallicence Carbonimidothioates nationallicence Phosphanegold thiolates nationallicence Apoptosis nationallicence Nuclear factor-κB activation pathway nationallicence Ooi Kah Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut Yeo Chien Department of Chemistry, University of Malaya, 50603, Kuala Lumpur, Malaysia aut Ang Kok-Pian Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut Akim Abdah Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut Cheah Yoke-Kqueen Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut Halim Siti Department of Chemistry, University of Malaya, 50603, Kuala Lumpur, Malaysia aut Seng Hoi-Ling Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut Tiekink Edward Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 855-873 0949-8257 20:5<855 2015 20 775 https://doi.org/10.1007/s00775-015-1271-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1271-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ooi Kah Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut NATIONALLICENCE 700 1- Yeo Chien Department of Chemistry, University of Malaya, 50603, Kuala Lumpur, Malaysia aut NATIONALLICENCE 700 1- Ang Kok-Pian Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut NATIONALLICENCE 700 1- Akim Abdah Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut NATIONALLICENCE 700 1- Cheah Yoke-Kqueen Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut NATIONALLICENCE 700 1- Halim Siti Department of Chemistry, University of Malaya, 50603, Kuala Lumpur, Malaysia aut NATIONALLICENCE 700 1- Seng Hoi-Ling Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut NATIONALLICENCE 700 1- Tiekink Edward Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 855-873 0949-8257 20:5<855 2015 20 775