title: Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect.
abstract: 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.
authors.affiliation: INSERM, UMR991, CHRU Pontchaillou, 35033 Rennes, France; Université de Rennes1, 35043 Rennes, France; SATT Ouest Valorisation, 14C rue du Pâtis Tatelin, 35704 Rennes, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Renaud
authors.affiliation: INSERM, UMR991, CHRU Pontchaillou, 35033 Rennes, France; Université de Rennes1, 35043 Rennes, France; LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Corcé
authors.affiliation: INSERM, UMR991, CHRU Pontchaillou, 35033 Rennes, France; Université de Rennes1, 35043 Rennes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cannie
authors.affiliation: Laboratoire de Biologie Générale et Enzymologie, CHRU Pontchaillou, 35033 Rennes, France; Université de Rennes1, 35043 Rennes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Ropert
authors.affiliation: Laboratoire de toxicologie, CHRU Pontchaillou, 35033 Rennes, France; Université de Rennes1, 35043 Rennes, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lepage
authors.affiliation: INSERM, UMR991, CHRU Pontchaillou, 35033 Rennes, France; Université de Rennes1, 35043 Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
authors.affiliation: LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2, rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
authors.forename: David
authors.initials: D
authors.lastname: Deniaud
authors.affiliation: INSERM, UMR991, CHRU Pontchaillou, 35033 Rennes, France; Université de Rennes1, 35043 Rennes, France. Electronic address: francois.gaboriau@univ-rennes1.fr.
authors.forename: François
authors.initials: F
authors.lastname: Gaboriau
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D011073:Polyamines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007502:Iron Chelating Agents; D011073:Polyamines; D000518:Eflornithine
keywords: Cancer; Colon adenocarcinoma; Iron; Iron chelator; Polyamine; Polyamine transport system; Tumor vectorization