title: Neolignans from Nectandra megapotamica (Lauraceae) Display in vitro Cytotoxic Activity and Induce Apoptosis in Leukemia Cells.
abstract: Nectandra megapotamica (Spreng.) Mez. (Lauraceae) is a well-known Brazilian medicinal plant that has been used in folk medicine to treat several diseases. In continuation of our ongoing efforts to discover new bioactive natural products from the Brazilian flora, this study describes the identification of cytotoxic compounds from the MeOH extract of N. megapotamica (Lauraceae) leaves using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of eight tetrahydrofuran neolignans: calopeptin (1), machilin-G (2), machilin-I (3), aristolignin (4), nectandrin A (5), veraguensin (6), ganschisandrin (7), and galgravin (8). Different assays were conducted to evaluate their cytotoxic activities and to determine the possible mechanism(s) related to the activity displayed against human leukemia cells. The most active compounds 4, 5 and 8 gave IC50 values of 14.2 ± 0.7, 16.9 ± 0.8 and 16.5 ± 0.8 µg/mL, respectively, against human leukemia (HL-60) tumor cells. Moreover, these compounds induced specific apoptotic hallmarks, such as plasma membrane bleb formation, nuclear DNA condensation, specific chromatin fragmentation, phosphatidyl-serine exposure on the external leaflet of the plasma membrane, cleavage of PARP as well as mitochondrial damage, which as a whole could be related to the intrinsic apoptotic pathway.
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil. vitor.ponci@gmail.com.
authors.forename: Vitor
authors.initials: V
authors.lastname: Ponci
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP 04023-062, Brazil. camyla.ff@gmail.com.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Figueiredo
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP 04023-062, Brazil. mari.massa@gmail.com.
authors.forename: Mariana H
authors.initials: MH
authors.lastname: Massaoka
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP 04023-062, Brazil. camyla.ff@gmail.com.
authors.forename: Camyla F
authors.initials: CF
authors.lastname: de Farias
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP 04023-062, Brazil. alisson@gmail.com.
authors.forename: Alisson L
authors.initials: AL
authors.lastname: Matsuo
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil. psartorelli@unifesp.br.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sartorelli
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972-270, Brazil. joao.lago@unifesp.br.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001938:Brazil; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D019770:Lauraceae / Q000737:chemistry*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D061986:MCF-7 Cells; D008546:Melanoma, Experimental; D051379:Mice; D009928:Organ Specificity; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry*; D010946:Plants, Medicinal; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism; D059748:Proteolysis; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003603:Cytotoxins; D017705:Lignans; D010718:Phosphatidylserines; D010936:Plant Extracts; D011065:Poly(ADP-ribose) Polymerases
keywords: Lauraceae; Nectandra megapotamica; apoptosis; cytotoxic effect; neolignans