Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

• Published in: Environmental research 2015-07, Vol.140, p.18-31
• Main Authors: Bedia, Carmen, Dalmau, Núria, Jaumot, Joaquim, Tauler, Romà
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ALDRIN; Base Sequence; BIOLOGICAL PATHWAYS; Cancer; CARDIOLIPIN; Cell Line, Tumor; Chemometrics; Chromatography, Liquid; CHRONIC EXPOSURE; COMPARATIVE EVALUATIONS; DNA Primers; Endocrine disruptors; Endocrine Disruptors - toxicity; Epithelial-Mesenchymal Transition; Exposure; Formations; HORMONES; Humans; LEAST SQUARE FIT; LECITHINS; Lipids; Lipids - analysis; Male; Mass Spectrometry; NEOPLASMS; PHENOTYPE; Phospholipids; POLYCHLORINATED BIPHENYLS; PROSTATE; Prostate cancer; Prostatic Neoplasms - pathology; Real-Time Polymerase Chain Reaction; TRIGLYCERIDES; Untargeted lipidomics
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2015.03.014

Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. [Display omitted] •Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells.•An untargeted lipidomic analysis has been performed on chronic exposed cells.•Lipidomic results showed changes in specific lipid species under chronic exposure.•These lipids may have a role in the acquisition of a malignant phenotype.