title: Different cell death responses induced by eupomatenoid-5 in MCF-7 and 786-0 tumor cell lines.
abstract: Natural products remain an important source of new drugs, including anticancer drugs. Recently, our group reported the anticancer activity of eupomatenoid-5 (eup-5), a neolignan isolated from Piper regnellii (Miq.) C. DC. var. regnellii leaves. In vitro studies demonstrated that MCF-7 (breast) and 786-0 (kidney) were among the cancer cell lines most sensitive to eup-5 treatment. The current results demonstrate that mitochondrial membrane depolarization and generation of reactive oxygen species are implicated in eup-5-mediated cytotoxic effects on these cancer cells lines. In MCF-7 cells, eup-5 led to phosphatidylserine externalization and caspase activation, whereas the same did not occur in 786-0 cells. Scanning electron microscopy revealed a reduction of microvilli density, as well as cell morphology alterations. Moreover, treated MCF-7 cells exhibited well-characterized apoptosis alterations, while treated 786-0 cells exhibited characteristics of programmed necroptosis process. These findings support the possibility that different mechanisms may be targeted by eup-5 in cell death response.
authors.affiliation: Programa de Pós-graduação em Biologia Celular e Estrutural, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-872, SP, Brazil; Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), UNICAMP, Campinas 13083-970, SP, Brazil. Electronic address: giovannabl@yahoo.com.br.
authors.forename: Giovanna Barbarini
authors.initials: GB
authors.lastname: Longato
authors.affiliation: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), UNICAMP, Campinas 13083-970, SP, Brazil.
authors.forename: Giovanna Francisco
authors.initials: GF
authors.lastname: Fiorito
authors.affiliation: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), UNICAMP, Campinas 13083-970, SP, Brazil.
authors.forename: Débora Barbosa
authors.initials: DB
authors.lastname: Vendramini-Costa
authors.affiliation: Divisão de Fitoquímica, CPQBA, UNICAMP, Campinas 13083-970, SP, Brazil.
authors.forename: Ilza Maria
authors.initials: IM
authors.lastname: de Oliveira Sousa
authors.affiliation: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), UNICAMP, Campinas 13083-970, SP, Brazil.
authors.forename: Sirlene Valério
authors.initials: SV
authors.lastname: Tinti
authors.affiliation: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), UNICAMP, Campinas 13083-970, SP, Brazil.
authors.forename: Ana Lúcia Tasca Gois
authors.initials: AL
authors.lastname: Ruiz
authors.affiliation: Laboratório de Imunopatologia Keizo Asami (LIKA) e Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil; Faculdade de Ciências, Educação e Tecnologia de Garanhuns (FACETEG), Universidade de Pernambuco (UPE), Garanhuns 55290-000, PE, Brazil.
authors.forename: Sinara Mônica Vitalino
authors.initials: SM
authors.lastname: de Almeida
authors.affiliation: Laboratório de Imunopatologia Keizo Asami (LIKA) e Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil.
authors.forename: Rafael José Ribeiro
authors.initials: RJ
authors.lastname: Padilha
authors.affiliation: Divisão de Fitoquímica, CPQBA, UNICAMP, Campinas 13083-970, SP, Brazil.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Foglio
authors.affiliation: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), UNICAMP, Campinas 13083-970, SP, Brazil; Faculdade de Ciências Farmacêuticas, UNICAMP, Campinas 13083-872, SP, Brazil.
authors.forename: João Ernesto
authors.initials: JE
authors.lastname: de Carvalho
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D031701:Piper; D018515:Plant Leaves; D013481:Superoxides / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D010636:Phenols; D010718:Phosphatidylserines; D013481:Superoxides; C452811:eupomatenoid 5; D006861:Hydrogen Peroxide; D020169:Caspases
keywords: 786-0; Apoptosis; Eupomatenoid-5; MCF-7; Piper regnellii; Programmed necrosis