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: Adilson Kleber Ferreira, Paulo Luiz de-Sá-Júnior, Kerly Fernanda Mesquita Pasqualoto, Ricardo Alexandre de Azevedo, Diana Aparecida Dias Câmara, André Santos Costa, Carlos Rogério Figueiredo, Alisson Leonardo Matsuo, Mariana Hiromi Massaoka, Aline Vivian Vatti Auada, Ivo Lebrun, Mariana Celestina Frojuello Costa Bernstorff Damião, Maurício Temotheo Tavares, Fátima Maria Motter Magri, Irina Kerkis, Roberto Parise Filho
• Journal: Biochimie (Biochimie) Vol. 99 Pg. 195-207 (Apr 2014) ISSN: 1638-6183 [Electronic] France
• PMID: 24355203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Allyl Compounds
• Antineoplastic Agents, Phytogenic
• Dioxoles
• Plant Extracts
• 5-allyl 6,7-dimethoxy 1,3-benzodioxole
• Electron Transport Complex IV
• CASP3 protein, human
• Caspase 3

Topics

• Allyl Compounds (chemistry, isolation & purification, pharmacology)
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Calcium Signaling
• Caspase 3 (metabolism)
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Cytoskeleton (drug effects, metabolism, pathology)
• Dioxoles (chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• Electron Transport Complex IV (metabolism)
• Gas Chromatography-Mass Spectrometry
• Humans
• MCF-7 Cells
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Molecular Dynamics Simulation
• Oxidative Stress (drug effects)
• Piper (chemistry)
• Plant Extracts (chemistry, isolation & purification, pharmacology)