Document Detail

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.
MedLine Citation:
PMID:  25434100     Owner:  NLM     Status:  In-Process    
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.
Mihir Tanay Das; Manoj Kumar; Indu Shekhar Thakur
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Indian journal of experimental biology     Volume:  52     ISSN:  0019-5189     ISO Abbreviation:  Indian J. Exp. Biol.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0233411     Medline TA:  Indian J Exp Biol     Country:  India    
Other Details:
Languages:  eng     Pagination:  1052-61     Citation Subset:  IM    
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