title: Ferrocifen derivatives that induce senescence in cancer cells: selected examples.
abstract: Platinum coordination complexes represent an important class of anti-tumor agents. Due to recognized drawbacks, research into other types of metallodrugs has been diversified with the aim of finding new chemical entities with alternative mechanisms of action to overcome classical chemoresistance. P5 and DP1, two closely related ferrocenyl complexes bearing a similar ferrocenyl-ene-phenyl motif and displaying marked differences in their conformations and oxidation state versatility, were assayed in cancer cell models characterized by various sensitivities to pro-apoptotic stimuli. P5 and DP1 exert growth inhibitory effects between 0.5 and 10 μM against glioma and melanoma cells including pluripotent stem-like cells. These effects are due, at least partly, to senescence induction with typical SA-β-galactosidase staining and senescence-associated secretory phenotype (SASP) as measured by the secretion of IL-1α, IL-1β, IL-6, IL-8 and TNF-α. Regulation of these cytokines' secretion may be related to AP-1 and other transcription factors unrelated to senescence. An in vivo graft of B16F10 cells after in vitro pre-incubation with DP1 or P5 led to increased survival in mice. In conclusion, P5 and DP1 ferrocenyl complexes induce senescence in various cancer cell models associated with distinct sensitivity to pro-apoptotic stimuli.
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium; Chimie ParisTech, 75005 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bruyère
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: vemathie@ulb.ac.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, IPCM UMR 8232, F-75005 Paris, France; CNRS, UMR 8232, IPCM, F-75005 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vessières
authors.affiliation: Chimie ParisTech, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, IPCM UMR 8232, F-75005 Paris, France; CNRS, UMR 8232, IPCM, F-75005 Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigeon
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, IPCM UMR 8232, F-75005 Paris, France; CNRS, UMR 8232, IPCM, F-75005 Paris, France.
authors.forename: Siden
authors.initials: S
authors.lastname: Top
authors.affiliation: Chimie ParisTech, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, IPCM UMR 8232, F-75005 Paris, France; CNRS, UMR 8232, IPCM, F-75005 Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Jaouen
authors.affiliation: Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D005296:Ferrous Compounds; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C514120:ferrocifen; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase
keywords: Anti-cancer effects; Cytokine; Ferrocene; Metallodrug; Senescence