title: In vitro and in vivo studies of the antineoplastic activity of copper (II) compounds against human leukemia THP-1 and murine melanoma B16-F10 cell lines.
abstract: We investigated the antineoplastic activities of a previously reported copper (II) coordination compound, [Cu(BMPA)Cl2]CH3OH (1), and a new compound, [Cu(HBPA)Cl2]H2O (2), where BMPA is bis(pyridin-2-ylmethyl)amine and HBPA is (2-hydroxybenzyl)(2-pyridylmethyl)amine, using various cellular models of human leukemia (THP-1, U937, HL60, Molt-4, JURKAT) and human colon cancer (COLO 205), as well as a murine highly metastatic melanoma (B16-F10) cell line. Compound (2) was characterized using several physical and chemical techniques, including X-ray diffraction studies. The IC50 values of the copper coordination complexes in the human leukemia cell lines ranged from 87.63 ± 1.02 to ≥400 μM at high cell concentrations and from 19.17 ± 1.06 to 97.67 ± 1.23 μM at low cell concentrations. Both compounds induced cell death, which was determined by cell cycle analyses and phosphatidylserine exposure studies. THP-1 cells released cytochrome c to the cytoplasm 12 h after treatment with 400 μM of compound (2). To evaluate the apoptosis pathway induced by compound (2), we measured the activities of initiator caspases 8 and 9 and executioner caspases 3 and 6. The results were suggestive of the activation of both intrinsic and extrinsic apoptosis pathways. To investigate the activities of the compounds in vivo, we selected two sensitive cell lines from leukemia (THP-1) and solid tumor (B16-F10) lineages. BALB/c nude bearing THP-1 tumors treated with 12 mg·kg(-1) of compound (2) showed a 92.4% inhibition of tumor growth compared with the control group.
authors.affiliation: LBR/CBB - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Layla J H
authors.initials: LJH
authors.lastname: Borges
authors.affiliation: LCQUI/CCT - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Érika S
authors.initials: ÉS
authors.lastname: Bull
authors.affiliation: LCQUI/CCT - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Christiane
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: LCQUI/CCT - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Horn
authors.affiliation: LCQUI/CCT - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Nathalia F
authors.initials: NF
authors.lastname: Azeredo
authors.affiliation: Laboratório de Difração de Raios X, Universidade Federal Fluminense (UFF), Niterói, RJ, Brazil.
authors.forename: Jackson A L C
authors.initials: JALC
authors.lastname: Resende
authors.affiliation: LBR/CBB - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil; UNIVASF - Universidade Federal do Vale do São Francisco, Brazil.
authors.forename: William R
authors.initials: WR
authors.lastname: Freitas
authors.affiliation: LSA/CCTA - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Eulógio C Q
authors.initials: ECQ
authors.lastname: Carvalho
authors.affiliation: LSA/CCTA - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Lemos
authors.affiliation: LSA/CCTA - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil.
authors.forename: Hassan
authors.initials: H
authors.lastname: Jerdy
authors.affiliation: LBR/CBB - Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ, Brazil. Electronic address: hiko.kanashiro@gmail.com.
authors.forename: Milton M
authors.initials: MM
authors.lastname: Kanashiro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011725:Pyridines
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D056831:Coordination Complexes; D011725:Pyridines; C538976:bis(pyridin-2-ylmethyl)amine; D003300:Copper
keywords: Antineoplastic activity; Apoptosis; Copper (II) complex; Leukemia; Melanoma