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Paper Information

Title: 

EFFECT OF ZEARALENONE ON CYTOCHROME P450 1A1 IN TCCD-INDUCED MCF-7 HUMAN BREAST CANCER CELLS

Type: SPEECH
Author(s): MALEKINEZHAD H.*,FINK G.J.
 
 *DEPT. OF VETERINARY, PHARMACOLOGY, PHARMACY AND TOXICOLOGY, FACULTY OF VETERINARY MEDICINE, UTRECHT UNIVERSITY, 3508 TD UTRECHT, THE NETHERLANDS
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Introduction: The mycoestrogen zearalenone (ZEA) is found worldwide as contaminant on cereals and grains. ZEA activates estrogen receptors resulting in functional and morphological alteration in reproductive organs. As many of environmental contaminants including polycyclic aromatic hydrocarbons and polyhalogenated dioxins exert their toxic effects by binding and activating of aryl hydrocarbon receptors (AhR), there is lack of knowledge to figure out the clear mechanistic pathway(s) of ZEA action. Hence, in this study possible transcriptional pathway of ZEA action in MCF-7 cells was investigated.
Methods: as among the other inducible target genes for AhR, the expression of cytochrome P450 1A1 (CYP1A1) depends on the AhR activity, thus we conducted a series of experiment including Ethoxyresorrufin O-deethylation (EROD) assay to measure CYP 1A1 activity in TCDD-induced MCF-7 cells under E2 and ZEA treatment. Subsequently, any alteration in mRNA level of CYP1A1 and AhR in TCDD-induced and control MCF-7 cells was investigated by means of quantitive PCR (QPCR).
Results: The exposed MCF-7 cells against 10nM TCDD showed huge induction in CYP1 activities in comparison to control (DMSO treated) cells. Moreover, exposing TCDD-induced cells against E2, ZEA, for 48 h reduced EROD activities significantly (P < 0.05). Moreover, treatment of TCDD-induced cells with E2 and ZEA decreased CYP1A1 mRNA level dramatically and increased slightly the mRNA level of AhR.
Conclusion: Cytochrome P450s catalyse the metabolism of steroids, and a number of other endocrine and autocrine substances. Human CYP1A1 and 1B1 play major role in the metabolism of oestrogens to catechol estrogens. Our results showed that like as E2, ZEA decreased dramatically EROD-activity. This finding is not consisting with estrogenic potency of given compounds as E2 exerts the strongest estrogenecity and followed by ZEA. According to obtained results from QPCR studies, both E2 and ZEA lowered CYP 1A1 and increased significantly AhR mRNA levels, respectively. Thus it is logic to conclude that among the other possible transcriptional pathways including estrogen receptors pathway, ZEA mediate its effects via CYP 1A1 and AhR in human breast cancer cells. As CYP1A1 plays a critical role in estrogens metabolism as a protective role, thus this study may raise this concern that ZEA could be considered to subjected as a carcinogenic compound in human and animal life.

 
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