Christian Gaiddon

Inserm

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Michel Pfeffer

Centre National de la Recherche Scientifique

Jean‐Philippe Loeffler

Inserm

Christophe Orvain

Université de Strasbourg

Georg Mellitzer

Université de Strasbourg

Isabelle Groß

Université de Strasbourg

Claude B. Sirlin

University of California, San Diego

Ronan Le Lagadec

Universidad Nacional Autónoma de México

Samir Benosman

Sanford Burnham Prebys Medical Discovery Institute

Maria V. Babak

City University of Hong Kong

Cynthia Licona

Université de Strasbourg

Cooperative Institutions

Université de Strasbourg

186

Centre National de la Recherche Scientifique

177

Inserm

146

Institut de Chimie

Institut de Chimie de Strasbourg

Institut de génétique et de biologie moléculaire et cellulaire

Shanghai Jiao Tong University

Hôpitaux Universitaires de Strasbourg

Institut de Cancérologie Strasbourg

Institut de Recherche contre les Cancers de l’Appareil Digestif

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Front Cover: Synthesis of Cytotoxic Iron‐Containing Macrocycles Through Unexpected C(sp²)−C(sp²) Bonds Formation (Eur. J. Inorg. Chem. 23/2023)

European Journal of Inorganic Chemistry (2023)

Carolina Torres‐Gutiérrez Aldo S. Estrada‐Montaño Christophe Orvain Georg Mellitzer Christian Gaiddon

The Front Cover shows a representation of stomach cancer cells being destroyed by an iron(II) complex bearing a tetradentate ligand. Gastric cancer is associated with a high mortality rate and high lethality and is frequently resistant to standard chemotherapies and immunotherapy. A cutting-edge reaction between Fe3(CO)12 and brominated or mercurated pincer derivatives promotes the formation of carbon−carbon bonds, and a 16-electron iron(II) complex with a tetradentate ligand originating from the dimerization of 6-phenyl-2,2′-bipyridine and a protonated 14-membered macrocycle from 2,6-diphenyl-pyridine were obtained. These new compounds are cytotoxic towards stomach cancer cells. Thanks to the presence of the iron center, the biological activity dramatically increased, and the complex was 5-fold more toxic than cisplatin on AGS cells. The cover was designed by Carolina Torres-Gutiérrez (the first author) and Hortensia Segura Silva. More information can be found in the Research Article by R. Le Lagadec and co-workers.

Front cover

10.1002/ejic.202300362

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A Subset of Tumor-Derived Mutant Forms of p53 Down-Regulate p63 and p73 through a Direct Interaction with the p53 Core Domain

Molecular and Cellular Biology (2001)

Christian Gaiddon Maria Lokshin Jin-Woo Ahn T. Zhang Carol Prives

The p53 protein is related by sequence homology and function to the products of two other genes, p63 and p73, that each encode several isoforms. We and others have discovered previously that certain tumor-derived mutants of p53 can associate and inhibit transcriptional activation by the α and β isoforms of p73. In this study we have extended these observations to show that in transfected cells a number of mutant p53 proteins could bind and down-regulate several isoforms not only of p73 (p73α, -β, -γ, and -δ) but also of p63 (p63α and -γ; ΔNp63α and -γ). Moreover, a correlation existed between the efficiency of p53 binding and the inhibition of p63 or p73 function. We also found that wild-type p63 and p73 interact efficiently with each other when coexpressed in mammalian cells. The interaction between p53 mutants and p63 or p73 was confirmed in a physiological setting by examining tumor cell lines that endogenously express these proteins. We also demonstrated that purified p53 and p73 proteins interact directly and that the p53 core domain, but not the tetramerization domain, mediates this interaction. Using a monoclonal antibody (PAb240) that recognizes an epitope within the core domain of a subset of p53 mutants, we found a correlation between the ability of p53 proteins to be immunoprecipitated by this antibody and their ability to interact with p73 or p63 in vitro and in transfected cells. Based on these results and those of others, we propose that interactions between the members of the p53 family are likely to be widespread and may account in some cases for the ability of tumor-derived p53 mutants to promote tumorigenesis.

Immunoprecipitation

HEK 293 cells

10.1128/mcb.21.5.1874-1887.2001

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Citations (459)

Impact of cyclometalated ruthenium(II) complexes on lactate dehydrogenase activity and cytotoxicity in gastric and colon cancer cells

Journal of Inorganic Biochemistry (2016)

Hugo Rico Bautista Rafael Díaz Longzhu Q. Shen Christophe Orvain Christian Gaiddon

10.1016/j.jinorgbio.2016.07.014

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Citations (23)

Use of a case-mix approach to study the trends in the incidence of second primary cancers

Annals of Epidemiology (2018)

Boris Gass Émilie Marrer Simona Bara Karine Ligier F. Molinié

Case mix index

10.1016/j.annepidem.2018.02.008

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Citations (4)

Dibromine Promoted Transmetalation of an Organomercurial by Fe(CO)₅: Synthesis, Properties, and Cytotoxicity of Bis(2-C₆H₄-2′-py-κC,N)dicarbonyliron(II)

Organometallics (2020)

Aldo S. Estrada‐Montaño Alexandre Gries José A. Oviedo-Fortino Carolina Torres‐Gutiérrez Amira Grain-Hayton

Bis-cyclometalated iron(II) complex [Fe(κC,N-phpy)2(CO)2] (1) (phpyH = 2-phenylpyridine) has been prepared in good yield from [Fe(CO)5] and [Hg(phpy)2] in the presence of dibromine, which is unexpectedly a crucial component of the reaction mixture. It is needed for the generation of short-lived reactive intermediate [FeBr(CO)5]Br, which is actually involved in the electrophilic substitution reaction with [Hg(phpy)2]. When irradiated by visible light, compound 1 readily affords bis(2-(pyridine-2-yl)phenyl)methanone (2) and iron oxides through the insertion of CO in the Fe–C bond of the cyclometalated moiety. Structures of iron complex 1 and ketone 2 were confirmed by X-ray crystallography. Activation of [Fe(CO)5] by Br2 represents a new approach for generating an iron intermediate, which is active in transmetalation reactions. Cytotoxic activity of 1 was tested against three gastric cancer cell lines, KATO III, AGS, and NUGC3. The activity against KATO III and NUGC3 cells is moderate, while complex 1 displayed excellent cytotoxicity against AGS cells. The molecular mechanism investigation showed that the cytotoxic activity of 1 appears independent of caspase 3 and the TP53 tumor suppressor gene, suggesting an apoptotic-independent process.

Transmetalation

Moiety

10.1021/acs.organomet.0c00107

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Citations (6)

A Novel Near‐IR Absorbing Ruthenium(II) Complex as Photosensitizer for Photodynamic Therapy and its Cetuximab Bioconjugates

ChemBioChem (2023)

Marta Martínez‐Alonso Albert Gandioso Chloé Thibaudeau Xue Qin Philippe Arnoux

Abstract A novel Ru(II) cyclometalated photosensitizer (PS), Ru‐NH 2 , for photodynamic therapy (PDT) of formula [Ru(appy)(bphen) 2 ]PF 6 (where appy=4‐amino‐2‐phenylpyridine and bphen=bathophenanthroline) and its cetuximab (CTX) bioconjugates, Ru‐Mal‐CTX and Ru‐BAA‐CTX (where Mal=maleimide and BAA=benzoylacrylic acid) were synthesised and characterised. The photophysical properties of Ru‐NH 2 revealed absorption maxima around 580 nm with an absorption up to 725 nm. The generation of singlet oxygen ( 1 O 2 ) upon light irradiation was confirmed with a 1 O 2 quantum yield of 0.19 in acetonitrile. Preliminary in vitro experiments revealed the Ru‐NH 2 was nontoxic in the dark in CT‐26 and SQ20B cell lines but showed outstanding phototoxicity when irradiated, reaching interesting phototoxicity indexes (PI) >370 at 670 nm, and >150 at 740 nm for CT‐26 cells and >50 with NIR light in SQ20B cells. The antibody CTX was successfully attached to the complexes in view of the selective delivery of the PS to cancer cells. Up to four ruthenium fragments were anchored to the antibody (Ab), as confirmed by MALDI‐TOF mass spectrometry. Nonetheless, the bioconjugates were not as photoactive as the Ru‐NH 2 complex.

Phototoxicity

Bioconjugation

10.1002/cbic.202300203

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Citations (11)

Evaluation of the Ability of an Organic Derivative of Ruthenium(II) to Reinforce the Cytotoxicity of Fast Neutron Against Malignant Cells in Culture

Letters in Drug Design & Discovery (2008)

Philip Bischoff L. Leyva Fouad Malek Sami Benzina J M Denis

The effect of combining RDC-11 (a new ruthenium organometallic complex) and fast neutrons (high-LET radiations) has been evaluated in RDM4 and U-87 tumor cell lines. After co-treatment, a substantial reduction of cell growth was recorded, which appears not to be correlated with the induction of apoptosis. Keywords: Ruthenium-based anticancer drugs, Apoptosis, High-LET radiation, Concomitant chemoradiotherapy, Fast neutrons

10.2174/157018008783406714

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Citations (5)

The tumor suppressor CDX2 opposes pro-metastatic biomechanical modifications of colon cancer cells through organization of the actin cytoskeleton

Cancer Letters (2016)

Nadine Platet Isabelle Hinkel Ludovic Richert Devadarssen Murdamoothoo Ahlam Moufok-Sadoun

CDX2

Metastasis suppressor

10.1016/j.canlet.2016.10.040

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Citations (30)

CCDC 617639: Experimental Crystal Structure Determination

The Cambridge Structural Database (2007)

L. Leyva Claude B. Sirlin Laia Rubio César V. Franco Ronan Le Lagadec

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

10.5517/ccnqpvw

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The atypical cadherin MUCDHL antagonizes colon cancer formation and inhibits oncogenic signaling through multiple mechanisms

Oncogene (2020)

Marine Beck Mathilde Baranger Ahlam Moufok-Sadoun Emilie Bersuder Isabelle Hinkel

10.1038/s41388-020-01546-y

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Citations (9)