Copper (II) and 2,2'-bipyridine complexation improves chemopreventive effects of naringenin against breast tumor cells

• Published in: PloS one 2014-09, Vol.9 (9), p.e107058
• Main Authors: Filho, Júlio César Conceição, Sarria, André Lúcio Franceschini, Becceneri, Amanda Blanque, Fuzer, Angelina Maria, Batalhão, Jaqueline Raquel, da Silva, Caio Marcio Paranhos, Carlos, Rose Maria, Vieira, Paulo Cezar, Fernandes, João Batista, Cominetti, Márcia Regina
• Format: Article
• Language: English
• Subjects: 2,2'-Dipyridyl - chemistry; 2,2'-Dipyridyl - pharmacology; 2,2'-Dipyridyl - therapeutic use; Analysis; Anticancer properties; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Antioxidants; Antiviral agents; Apoptosis; Bcl-2 protein; Biological effects; Biology and Life Sciences; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - prevention & control; Cancer; Cancer prevention; Cancer therapies; Caspase; Caspase-8; Caspase-9; Cell cycle; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - drug effects; Chemoprevention; Chemotherapy; Complexation; Coordination Complexes - pharmacology; Coordination Complexes - therapeutic use; Copper; Copper - chemistry; Copper - pharmacology; Copper - therapeutic use; Copper compounds; Cytometry; Deoxyribonucleic acid; DNA; Drug Evaluation, Preclinical; Drug Synergism; Drugs; Epidemiology; Female; Flavanones - pharmacology; Flavanones - therapeutic use; Flavonoids; Flow cytometry; Gelatinase B; Gene expression; Heavy metals; Humans; Inflammation; Inhibition; Isoflavones; Leukemia; Ligands; Medical prognosis; Naringenin; Pharmaceutical sciences; Physical Sciences; Tumor cells; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107058

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.