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

Ferreira A.K.; De-Sa-Junior P.L.; Pasqualoto K.F.M.; De Azevedo R.A.; Camara D.A.D.; Costa A.S.; Figueiredo C.R.; Matsuo A.L.; Massaoka M.H.; Auada A.V.V.; Lebrun I.; Damiao M.C.F.C.B.; Tavares M.T.; Magri F.M.M.; Kerkis I.; Parise Filho R.

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

item.page.type

Artigo

Date

2014

item.page.ispartof

Biochimie

item.page.citationsscopus

28

Authors

Ferreira A.K.
De-Sa-Junior P.L.
Pasqualoto K.F.M.
De Azevedo R.A.
Camara D.A.D.
Costa A.S.
Figueiredo C.R.
Matsuo A.L.
Massaoka M.H.
Auada A.V.V.
Lebrun I.
Damiao M.C.F.C.B.
Tavares M.T.
Magri F.M.M.
Kerkis I.
Parise Filho R.

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. © 2013 Elsevier Masson SAS. All rights reserved.