title: Casiopeina III-Ea, a copper-containing small molecule, inhibits the in vitro growth of primitive hematopoietic cells from chronic myeloid leukemia.
abstract: Several novel compounds have been developed for the treatment of different types of leukemia. In the present study, we have assessed the in vitro effects of Casiopeina III-Ea, a copper-containing small molecule, on cells from patients with Chronic Myeloid Leukemia (CML). We included primary CD34+Lineage-negative (Lin-) cells selected from CML bone marrow, as well as the K562 and MEG01 cell lines. Bone marrow cells obtained from normal individuals - both total mononuclear cells as well as CD34+Lin-cells- were used as controls. IC50 corresponded to 0.5μM for K562 cells, 0.63μM for MEG01 cells, 0.38μM for CML CD34+lin-cells, and 1.0μM for normal CD34+lin-cells. Proliferation and expansion were also inhibited to significantly higher extents in cultures of CML cells as compared to their normal counterparts. All these effects seemed to occur via a bcr-abl transcription-independent mechanism that involved a delay in cell division, an increase in cell death, generation of Reactive Oxygen Species and changes in cell cycle. Our results demonstrate that Casiopeina III-Ea possesses strong antileukemic activity in vitro, and warrant further preclinical (animal) studies to assess such effects in vivo.
authors.affiliation: Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security (IMSS), Mexico City, Mexico. Electronic address: acgtony@yahoo.com.mx.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Chavez-Gonzalez
authors.affiliation: Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security (IMSS), Mexico City, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Centeno-Llanos
authors.affiliation: Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security (IMSS), Mexico City, Mexico.
authors.forename: Dafne
authors.initials: D
authors.lastname: Moreno-Lorenzana
authors.affiliation: Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security (IMSS), Mexico City, Mexico.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Sandoval-Esquivel
authors.affiliation: Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security (IMSS), Mexico City, Mexico.
authors.forename: Socrates
authors.initials: S
authors.lastname: Aviles-Vazquez
authors.affiliation: School of Medicine, National Autonomous University of Mexico (UNAM), Mexico.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Bravo-Gomez
authors.affiliation: Inorganic and Nuclear Chemistry Department, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
authors.affiliation: Department of Hematology, La Raza Medical Center, IMSS, Mexico City, Mexico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ayala-Sanchez
authors.affiliation: Department of Hip Surgery, Villa Coapa General Hospital, IMSS, Mexico City, Mexico.
authors.forename: Hector
authors.initials: H
authors.lastname: Torres-Martinez
authors.affiliation: Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security (IMSS), Mexico City, Mexico. Electronic address: hmayaniv@prodigy.net.mx.
authors.forename: Hector
authors.initials: H
authors.lastname: Mayani
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000494:pharmacology*; D003300:Copper; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D010618:Phenanthrolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D014407:Tumor Cells, Cultured
chemical_list: C586191:(Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)(H2O))NO3; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D003300:Copper
keywords: Casiopeinas; Chronic myeloid leukemia; Leukemic stem cells elimination