title: Biflorin induces cytotoxicity by DNA interaction in genetically different human melanoma cell lines.
abstract: Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma.
authors.affiliation: Pharmaceutical Sciences, Federal University of Amazon, Av. General Rodrigo Octávio, 6200, Coroado, 69077-000 Manaus, Amazonas, Brazil; Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Rua Alexandre Amorim, 330, Aparecida, CEP: 69010-300, Manaus, Amazonas, Brazil.
authors.forename: Ana Carolina Lima
authors.initials: ACL
authors.lastname: Ralph
authors.affiliation: Center on Oncology Research, Federal University of Pará, PA, Brazil; Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Av. Mundurucus, 4487, Guamá, 66073-000, Belém, PA, Brazil. Electronic address: danicalcagno@gmail.com.
authors.forename: Danielle Queiroz
authors.initials: DQ
authors.lastname: Calcagno
authors.affiliation: Department of Organic and Inorganic Chemistry, Federal University of Ceará, Ceará, Brazil. Electronic address: luci.gregorio@yahoo.com.br.
authors.forename: Luciana Gregório
authors.initials: LG
authors.lastname: da Silva Souza
authors.affiliation: Department of Organic and Inorganic Chemistry, Federal University of Ceará, Ceará, Brazil. Electronic address: tlemos@dqoi.ufc.br.
authors.forename: Telma Leda Gomes
authors.initials: TLG
authors.lastname: de Lemos
authors.affiliation: Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Av. Mundurucus, 4487, Guamá, 66073-000, Belém, PA, Brazil. Electronic address: rcm.montenegro@gmail.com.
authors.forename: Raquel Carvalho
authors.initials: RC
authors.lastname: Montenegro
authors.affiliation: Genetic Division, Federal University of São Paulo, Rua Botucatu 740, Vila Clementino, 04023-062 São Paulo, SP, Brazil; Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu 740, Vila Clementino, 04023-062 São Paulo, SP, Brazil. Electronic address: macsmith@epm.br.
authors.forename: Marília
authors.initials: M
authors.lastname: de Arruda Cardoso Smith
authors.affiliation: Pharmaceutical Sciences, Federal University of Amazon, Av. General Rodrigo Octávio, 6200, Coroado, 69077-000 Manaus, Amazonas, Brazil; Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Av. General Rodrigo Octávio 6200, Coroado I, 69077-000 Manaus, Amazonas, Brazil. Electronic address: marne@ufam.edu.br.
authors.forename: Marne Carvalho
authors.initials: MC
authors.lastname: de Vasconcellos
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009285:Naphthoquinones / Q000633:toxicity*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D009285:Naphthoquinones; C084355:RRAD protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C522781:biflorin; D004247:DNA; D015254:DNA Modification Methylases; C000600377:TYMS protein, human; D013940:Thymidylate Synthase; C515491:MGMT protein, human; C484610:MELK protein, human; C482119:BRAF protein, human; D017346:Protein Serine-Threonine Kinases; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D018631:ras Proteins; D045643:DNA Repair Enzymes
keywords: Biflorin; Cell cycle progression; Human melanoma; Repair genes; Replication genes; SK-Mel