Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect
| Autor: | Olivier Loréal, Martine Ropert, François Gaboriau, Sylvie Lepage, Vincent Corcé, Isabelle Cannie, David Deniaud, Stéphanie Renaud |
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| Přispěvatelé: | Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Société d'Accélération du Transfert de Technologies (SATT OUEST VALORISATION), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), CHU Pontchaillou [Rennes], Laboratoire de Toxicologie Biologique et Médico-Légale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], This work was supported by the development funds SATT Ouest-Valorisation and FEDER Europe (Brittany region). The authors are grateful to the Conseil Régional Pays de la Loire, to the French Ministry of Education, to the Ligue Nationale contre le Cancer (LNCC, Ille et Vilaine/Loire Atlantique), to the Association pour la Recherche sur le Cancer (ARC) and to the Centre National de la Recherche Scientifique (CNRS) for financial support.The authors thank P. Loyer (Inserm UMR991, Rennes, France) and I. Morel (CHU Pontchaillou, Rennes, France) for scientific assistance in the flow cytometry and LC/MSMS analyses, respectively.In vivo experiments were carried out in the animal handling facility of the university, the ARCHE platform of the Structure Fédérative de Recherche BIOSIT in Rennes (BiogenOuest and Cancéropôle Grand Ouest network).The histological analysis were carried out in the histopathological platform H2P2 of the Structure Fédérative de Recherche BIOSIT in Rennes (BiogenOuest and Cancéropôle Grand Ouest network)., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Jonchère, Laurent |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MESH: Colonic Neoplasms/pathology
[SDV]Life Sciences [q-bio] MESH: Colonic Neoplasms/drug therapy Endogeny polyamine transport system Biochemistry Mice chemistry.chemical_compound 0302 clinical medicine MESH: Biological Transport/drug effects polyamine MESH: Molecular Targeted Therapy Polyamines MESH: Animals Molecular Targeted Therapy Cancer 0303 health sciences Iron chelator Chemistry MESH: Antineoplastic Agents/pharmacology Cell Cycle MESH: Iron Chelating Agents/pharmacology DNA Neoplasm Cell cycle Tumor Burden 3. Good health [SDV] Life Sciences [q-bio] 030220 oncology & carcinogenesis Colonic Neoplasms Female Intracellular MESH: Cell Cycle/drug effects Eflornithine Cell Survival MESH: DNA Neoplasm/antagonists & inhibitors MESH: HCT116 Cells Iron Transplantation Heterologous Mice Nude Antineoplastic Agents [SDV.CAN]Life Sciences [q-bio]/Cancer Iron Chelating Agents 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer In vivo MESH: Mice Nude Animals Humans MESH: Mice 030304 developmental biology Pharmacology Polyamine transport Cell growth MESH: DNA Neoplasm/biosynthesis Biological Transport MESH: Colonic Neoplasms/metabolism HCT116 Cells In vitro MESH: Eflornithine/pharmacology colon adenocarcinoma tumor vectorization Cancer research MESH: Polyamines/antagonists & inhibitors Polyamine MESH: Cell Survival/drug effects MESH: Female Neoplasm Transplantation MESH: Neoplasm Transplantation |
| Zdroj: | Biochemical Pharmacology Biochemical Pharmacology, Elsevier, 2015, 96 (3), pp.179-189. ⟨10.1016/j.bcp.2015.06.001⟩ Biochemical Pharmacology, 2015, 96 (3), pp.179-189. ⟨10.1016/j.bcp.2015.06.001⟩ |
| ISSN: | 0006-2952 1873-2968 |
| DOI: | 10.1016/j.bcp.2015.06.001⟩ |
| Popis: | International audience; Tumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine chain, is related to its high selectivity for the Polyamine Transport System (PTS), allowing its preferential uptake by tumoral cells. The difference in PTS activation between healthy cells and tumor cells enables tumor cells to be targeted, whereas the strong dependence of these cells on iron ensures a secondary targeting. Here, we demonstrated in vitro that HQ1-44 inhibits DNA synthesis and cell proliferation of HCT116 cells by modulating the intracellular metabolism of both iron and polyamines. Moreover, in vivo, in xenografted athymic nude mice, we found that HQ1-44 was as effective as cis-platin in reducing HCT116 tumor growth, without its side effects. Furthermore, as suggested by in vitro data, the depletion in exogenous or endogenous polyamines, known to activate the PTS, dramatically enhanced the antitumor efficiency of HQ1-44. These data support the need for further studies to assess the value of HQ1-44 as an adjuvant treatment in cancer |
| Databáze: | OpenAIRE |
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