title: Cytotoxic effects of dillapiole on MDA-MB-231 cells involve the induction of apoptosis through the mitochondrial pathway by inducing an oxidative stress while altering the cytoskeleton network.
abstract: Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Here, we have demonstrated for the first time that dillapiole has broad cytotoxic effects against a variety tumor cells. For instance, we found that it can act as a pro-oxidant compound through the induction of reactive oxygen species (ROS) release in MDA-MB-231 cells. We also demonstrated that dillapiole exhibits anti-proliferative properties, arresting cells at the G0/G1 phase and its antimigration effects can be associated with the disruption of actin filaments, which in turn can prevent tumor cell proliferation. Molecular modeling studies corroborated the biological findings and suggested that dillapiole may present a good pharmacokinetic profile, mainly because its hydrophobic character, which can facilitate its diffusion through tumor cell membranes. All these findings support the fact that dillapiole is a promising anticancer agent.
authors.affiliation: Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: Adilson Kleber
authors.initials: AK
authors.lastname: Ferreira
authors.affiliation: Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil. Electronic address: paulsaj2001@yahoo.com.br.
authors.forename: Paulo Luiz
authors.initials: PL
authors.lastname: de-Sá-Júnior
authors.affiliation: Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: Kerly Fernanda Mesquita
authors.initials: KF
authors.lastname: Pasqualoto
authors.affiliation: Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: Ricardo Alexandre
authors.initials: RA
authors.lastname: de Azevedo
authors.affiliation: Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: Diana Aparecida Dias
authors.initials: DA
authors.lastname: Câmara
authors.affiliation: Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: André Santos
authors.initials: AS
authors.lastname: Costa
authors.affiliation: Experimental Oncology Unit (UNONEX), Microbiology, Immunology and Parasitology Dept, Federal University of São Paulo, Rua Botucatu 862, 04023-062 Sao Paulo, Brazil.
authors.forename: Carlos Rogério
authors.initials: CR
authors.lastname: Figueiredo
authors.affiliation: Experimental Oncology Unit (UNONEX), Microbiology, Immunology and Parasitology Dept, Federal University of São Paulo, Rua Botucatu 862, 04023-062 Sao Paulo, Brazil.
authors.forename: Alisson Leonardo
authors.initials: AL
authors.lastname: Matsuo
authors.affiliation: Experimental Oncology Unit (UNONEX), Microbiology, Immunology and Parasitology Dept, Federal University of São Paulo, Rua Botucatu 862, 04023-062 Sao Paulo, Brazil.
authors.forename: Mariana Hiromi
authors.initials: MH
authors.lastname: Massaoka
authors.affiliation: Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: Aline Vivian Vatti
authors.initials: AV
authors.lastname: Auada
authors.affiliation: Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: Ivo
authors.initials: I
authors.lastname: Lebrun
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Prof. Lineu Prestes Avenue, 580, 05508-000 Sao Paulo, Brazil.
authors.forename: Mariana Celestina Frojuello Costa Bernstorff
authors.initials: MC
authors.lastname: Damião
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Prof. Lineu Prestes Avenue, 580, 05508-000 Sao Paulo, Brazil.
authors.forename: Maurício Temotheo
authors.initials: MT
authors.lastname: Tavares
authors.affiliation: Center for Biological Sciences and Health (CCBS), Mackenzie Presbyterian University, Consolação Avenue, 930, 01302-907 Sao Paulo, Brazil.
authors.forename: Fátima Maria Motter
authors.initials: FM
authors.lastname: Magri
authors.affiliation: Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, 05503-900 Sao Paulo, Brazil.
authors.forename: Irina
authors.initials: I
authors.lastname: Kerkis
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Prof. Lineu Prestes Avenue, 580, 05508-000 Sao Paulo, Brazil. Electronic address: roberto.parise@usp.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: Parise Filho
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020013:Calcium Signaling; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004149:Dioxoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D003576:Electron Transport Complex IV / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D018384:Oxidative Stress / Q000187:drug effects*; D031701:Piper / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic; D004149:Dioxoles; D010936:Plant Extracts; C498255:5-allyl 6,7-dimethoxy 1,3-benzodioxole; D003576:Electron Transport Complex IV; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Antitumoral; Apoptosis; Cell cycle; Dillapiole; Molecular modeling; Piper aduncum; ROS