title: Copper (II) and 2,2'-bipyridine complexation improves chemopreventive effects of naringenin against breast tumor cells.
abstract: Cancer is the second leading cause of death worldwide and there is epidemiological evidence that demonstrates this tendency is emerging. Naringenin (NGEN) is a trihydroxyflavanone that shows various biological effects such as antioxidant, anticancer, anti-inflammatory, and antiviral activities. It belongs to flavanone class, which represents flavonoids with a C6-C3-C6 skeleton. Flavonoids do not exhibit sufficient activity to be used for chemotherapy, however they can be chemically modified by complexation with metals such as copper (Cu) (II) for instance, in order to be applied for adjuvant therapy. This study investigated the effects of Cu(II) and 2,2'-bipyridine complexation with naringenin on MDA-MB-231 cells. We demonstrated that naringenin complexed with Cu(II) and 2,2'-bipyridine (NGENCuB) was more efficient inhibiting colony formation, proliferation and migration of MDA-MB-231 tumor cells, than naringenin (NGEN) itself. Furthermore, we verified that NGENCuB was more effective than NGEN inhibiting pro-MMP9 activity by zymography assays. Finally, through flow cytometry, we showed that NGENCuB is more efficient than NGEN inducing apoptosis in MDA-MB-231 cells. These results were confirmed by gene expression analysis in real time PCR. We observed that NGENCuB upregulated the expression of pro-apoptotic gene caspase-9, but did not change the expression of caspase-8 or anti-apoptotic gene Bcl-2. There are only few works investigating the effects of Cu(II) complexation with naringenin on tumor cells. To the best of our knowledge, this is the first work describing the effects of Cu(II) complexation of a flavonoid on MDA-MB-231 breast tumor cells.
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Júlio César Conceição
authors.initials: JC
authors.lastname: Filho
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: André Lúcio Franceschini
authors.initials: AL
authors.lastname: Sarria
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Amanda Blanque
authors.initials: AB
authors.lastname: Becceneri
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Angelina Maria
authors.initials: AM
authors.lastname: Fuzer
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Jaqueline Raquel
authors.initials: JR
authors.lastname: Batalhão
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Caio Marcio Paranhos
authors.initials: CM
authors.lastname: da Silva
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Rose Maria
authors.initials: RM
authors.lastname: Carlos
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Paulo Cezar
authors.initials: PC
authors.lastname: Vieira
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: João Batista
authors.initials: JB
authors.lastname: Fernandes
authors.affiliation: Departamento de Gerontologia, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: Cominetti
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D056831:Coordination Complexes / Q000494:pharmacology* / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005260:Female; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056831:Coordination Complexes; D044950:Flavanones; D015082:2,2'-Dipyridyl; D003300:Copper; C005273:naringenin