title: Differential toxicological endpoints of di(2-ethylhexyl) phthalate (DEHP) exposure in MCF-7 and MDA-MB-231 cell lines: possible estrogen receptor alpha (ERalpha) independent modulations.
abstract: Wide spread use of Di-(2-ethylhexyl) phthalate (DEHP) has made it a ubiquitous contaminant in today's environment, responsible for possible carcinogenic and endocrine disrupting effects. In the present investigation an integrative toxicoproteomic approach was made to study the estrogenic potential of DEHP. In vitro experiments carried out with DEHP (0.1-100 microM) induced proliferations (E-screen assay) in human estrogen receptors-alpha (ERalpha) positive MCF-7 and ERalpha negative MDA-MB-231 breast cancer cells irrespective of their ERa status. Further, DEHP suppressed tamoxifen (a potent anti-breast cancer drug) induced apoptosis in both cell types as shown by flowcytometric cell cycle analysis. Label-free quantitative proteomics analysis of the cell secretome of both the cell lines indicated a wide array of stress related, structural and receptor binding proteins that were affected due to DEHP exposure. The secretome of DEHP treated MCF-7 cells revealed the down regulation of lactotransferrin, an ERalpha responsive iron transport protein. The results indicated that toxicological effects of DEHP did not follow an ERa signaling pathway. However, the differential effects in MCF-7 and MDA-MB-231 cell lines indicate that ERa might have an indirect modulating effect on DEHP induced toxicity.
authors.forename: Mihir
authors.initials: M
authors.lastname: Tanay Das
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Indu Shekhar
authors.initials: IS
authors.lastname: Thakur
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000502:physiology*; D004967:Estrogens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry / Q000295:instrumentation; D008832:Microchemistry / Q000295:instrumentation; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D040901:Proteomics; D013629:Tamoxifen / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: C506487:ESR1 protein, human; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D004967:Estrogens; C490098:LTF protein, human; D009363:Neoplasm Proteins; D013629:Tamoxifen; D004051:Diethylhexyl Phthalate; D007781:Lactoferrin