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
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- 作者：Adilson Kleber Ferreira ; Paulo Luiz de-S谩-J煤nior ; Kerly Fern ; a Mesquita Pasqualoto ; Ricardo Alex ; re de Azevedo ; Diana Aparecida Dias C芒mara ; Andr茅 Santos Costa ; Carlos Rog茅rio Figueiredo ; Alisson Leonardo Matsuo ; Mariana Hiromi Massaoka ; Aline Vivian Vatti Auada ; Ivo Lebrun ; Mariana Celestina Frojuello Costa Bernstorff Dami茫o ; Maur铆cio Temotheo Tavares ; F谩tima Maria Motter Magri ; Irina Kerkis ; Roberto Parise Filho
- 关键词：Piper aduncum ; Dillapiole ; Antitumoral ; Apoptosis ; Cell cycle ; ROS ; Molecular modeling
- 刊名：Biochimie
- 出版年：April, 2014
- 年：2014
- 卷：99
- 期：Complete
- 页码：195-207
- 全文大小：3495 K
文摘
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.