title: The in-vitro and in-vivo inhibitory activity of biflorin in melanoma.
abstract: Biflorin, an ortho-naphthoquinone, is an active compound found in the roots of Capraria biflora L. It has been reported that biflorin presents anticancer activity, inhibiting both tumor cell line growth in culture and tumor development in mice. The aim of this study was to examine the effectiveness of biflorin treatment using both in-vitro and in-vivo melanoma models. Biflorin displayed considerable cytotoxicity against all tested cell lines, with half maximal inhibitory concentration values ranging from 0.58 μg/ml in NCI H23 (human lung adenocarcinoma) to 14.61 μg/ml in MDA-MB-231 (human breast cancer) cell lines. In a second set of experiments using B16 melanoma cells as a model, biflorin reduced cell viability but did not cause significant increase in the number of nonviable cells. In addition, the DNA synthesis was significantly inhibited. Flow cytometry analysis showed that biflorin may lead to an apoptotic death in melanoma cells, inducing DNA fragmentation and mitochondria depolarization, without affecting membrane integrity. In B16 melanoma-bearing mice, administration of biflorin (25mg/day) for 10 days inhibited tumor growth, and also increased the mean survival rate from 33.3±0.9 days (control) to 44.5±3.4 days (treated). Our findings suggest that biflorin may be considered as a promising lead compound for designing new drugs to be used in the treatment of melanoma.
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.
authors.forename: Marne C
authors.initials: MC
authors.lastname: Vasconcellos
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bezerra
authors.forename: Aluísio M
authors.initials: AM
authors.lastname: Fonseca
authors.forename: Ana Jérsia
authors.initials: AJ
authors.lastname: Araújo
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Telma L G
authors.initials: TL
authors.lastname: Lemos
authors.forename: Letícia V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Montenegro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009285:Naphthoquinones / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009285:Naphthoquinones; C522781:biflorin