title: A novel o-naphtoquinone inhibits N-cadherin expression and blocks melanoma cell invasion via AKT signaling.
abstract: The down-regulation or loss of epithelial markers is often accompanied by the up-regulation of mesenchymal markers. E-cadherin generally suppresses invasiveness, whereas N-cadherin promotes invasion and metastasis in vitro. The aim of this work is to investigate the role of biflorin, a naphthoquinone with proven anticancer properties, on the expression of N-cadherin and AKT proteins in MDA-MB-435 invasive melanoma cancer cells after 12h of exposure to 1, 2.5 and 5 μM biflorin. Biflorin inhibited MDA-MB-435 invasion in a dose-dependent manner (p<0.01). Likewise, biflorin down-regulated N-cadherin and AKT-1 expression in a dose-dependent manner. Biflorin did not inhibit the adhesion of MDA-MB-435 cells to any tested substrates. Additionally, biflorin blocked the invasiveness of cells by down-regulating N-cadherin, most likely via AKT-1 signaling. As such, biflorin may be a novel anticancer agent and a new prototype for drug design.
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa 01-Guamá, Belém/PA, Brazil. Electronic address: rcm.montenegro@gmail.com.
authors.forename: Raquel Carvalho
authors.initials: RC
authors.lastname: Montenegro
authors.forename: Marne Carvalho
authors.initials: MC
authors.lastname: de Vasconcellos
authors.forename: Gleyce Dos Santos
authors.initials: Gdos S
authors.lastname: Barbosa
authors.forename: Rommel M R
authors.initials: RM
authors.lastname: Burbano
authors.forename: Luciana G S
authors.initials: LG
authors.lastname: Souza
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
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009285:Naphthoquinones / Q000009:adverse effects / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D009285:Naphthoquinones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C522781:biflorin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT-1; Biflorin; Invasion inhibition; Melanoma; N-cadherin