title: Biological study of the effect of water soluble [N-(2-hydroxybenzyl)-L-aspartato] gallium complexes on breast carcinoma and fibrosarcoma cells.
abstract: Two water soluble gallium complexes described as [Ga(III)LCl], where L is the deprotonated form of N-2-hydroxybenzyl aspartic acid derivatives, were synthesized and characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry, and elemental analysis. The 2-(5-chloro-2-hydroxybenzylamino)succinic acid derivative (GS2) has been found to be a promising anticancer drug candidate. This compound was found to be more cytotoxic against human breast carcinoma MDA-MB231 and fibrosarcoma HT-1080 cell lines than the unsubstituted derivative and GaCl3. GS2 was able to induce apoptosis through downregulation of AKT phosphorylation, G2M arrest in cell cycle, and caspase 3/7 pathway. This gallium complex was found to induce an increase in mitochondrial ROS level in HT-1080 cells but not in MDA-MB231 cells. This suggests that the mechanism of action of GS2 would not be mediated by the drug-induced oxidative stress but probably by directly and indirectly inhibiting the AKT cell-signaling pathway.
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612) Faculté de Pharmacie, Université Paris-Saclay, 5, rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France.|Department of Biochemistry, Faculty of Science, Ain Shams University, Abbassia Square, Cairo, Egypt.|MEDyC-Unité CNRS UMR7369, SFR CAP-Santé FED4231UFR de Pharmacie, 51 rue Cognacq Jay, 51096, Reims Cedex, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mohsen
authors.affiliation: MEDyC-Unité CNRS UMR7369, SFR CAP-Santé FED4231UFR de Pharmacie, 51 rue Cognacq Jay, 51096, Reims Cedex, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Saby
authors.affiliation: Société de Coordination de Recherches Thérapeutiques (SCRT), 30, avenue du Port, 20220, Algajola, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Collery
authors.affiliation: Department of Biochemistry, Faculty of Science, Ain Shams University, Abbassia Square, Cairo, Egypt.
authors.forename: Gilane Mohamed
authors.initials: GM
authors.lastname: Sabry
authors.affiliation: Department of Biochemistry, Faculty of Science, Ain Shams University, Abbassia Square, Cairo, Egypt.
authors.forename: Rasha Elsherif
authors.initials: RE
authors.lastname: Hassan
authors.affiliation: Egyptian Petroleum Research Institute, Surfactant Laboratory, Nasr City, Cairo, Egypt.
authors.forename: Abdelfattah
authors.initials: A
authors.lastname: Badawi
authors.affiliation: MEDyC-Unité CNRS UMR7369, SFR CAP-Santé FED4231UFR de Pharmacie, 51 rue Cognacq Jay, 51096, Reims Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Jeannesson
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612) Faculté de Pharmacie, Université Paris-Saclay, 5, rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France. didier.desmaele@u-psud.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.affiliation: MEDyC-Unité CNRS UMR7369, SFR CAP-Santé FED4231UFR de Pharmacie, 51 rue Cognacq Jay, 51096, Reims Cedex, France. hamid.morjani@univ-reims.fr.
authors.forename: Hamid
authors.initials: H
authors.lastname: Morjani
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001224:Aspartic Acid / Q000737:chemistry*; D001943:Breast Neoplasms / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005354:Fibrosarcoma / Q000473:pathology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005708:Gallium / Q000737:chemistry*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D014867:Water; D001224:Aspartic Acid; D005708:Gallium; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053179:Caspase 7
keywords: Antitumor activity; Apoptosis; Gallium complex; Reactive oxygen species; Tridendate ligand