Antiproliferative effect of butyltin in MCF-7 cells
Jesper B Nielsen1, T H Rasmussen
1Environmental Medicine, Institute of Public Health, University of Southern Denmark, Winsløwparken 17, DK-5000 Odense, Denmark. jbnielsen@health.sdu.dk
Abstract:
Humans are exposed to tributyltin compounds primarily through the intake of marine food. Previous reports on toxic effects to humans are limited to a few in vitro studies giving conflicting results regarding their effects on the aromatase enzyme and androgen receptor (AR) responses. The present study evaluates the estrogenic potential of three butyltin compounds (mono-, di-, and tributyltin) in an in vitro system based on the E-Screen assay. None of the butyltin compounds tested was estrogenic in the concentration range assayed (0.01-1000 nM). However, both dibutyltin dichloride (DBT) (500 nM) and tributyltin chloride (TBT) (10 nM) inhibited 17beta-estradiol-induced cell proliferation. DBT (500 nM) and TBT (10 nM) also significantly reduced testosterone-induced cell proliferation, and the inhibition by TBT was rescued by increasing the concentration of testosterone. The present study did not confirm the inhibition of aromatase as the mechanism for an endocrine effect of butyltin compounds; moreover, the inhibition of cell proliferation by DBT and TBT occurred at concentrations at which no cytotoxicity was observed. The exact mechanism by which TBT and DBT inhibit cell proliferation remains unexplained, but it might be essentially independent of the estrogen receptor. Therefore, these compounds may not be termed classical endocrine disruptors, but rather as compounds that cause a functional anti-estrogenic response.
Insights
Tributyltin compounds in seafood do not act as estrogenic endocrine disruptors. Dibutyltin and tributyltin inhibit cell proliferation via a non-estrogen receptor pathway, suggesting a functional anti-estrogenic response.
Area of Science:
- Environmental Toxicology
- Endocrinology
- Marine Biology
Background:
- Human exposure to tributyltin (TBT) compounds occurs mainly through marine food consumption.
- Existing research on TBT's toxic effects on humans is limited, with conflicting in vitro findings on aromatase and androgen receptor (AR) responses.
Purpose of the Study:
- To evaluate the estrogenic potential of mono-, di-, and tributyltin compounds.
- To investigate the mechanism of endocrine disruption by butyltin compounds.
Main Methods:
- Utilized an in vitro E-Screen assay to assess estrogenic activity.
- Tested butyltin compounds (mono-, di-, tributyltin) in a concentration range of 0.01-1000 nM.
- Assessed effects on 17beta-estradiol and testosterone-induced cell proliferation.
Main Results:
- No estrogenic activity was observed for any tested butyltin compounds.
- Dibutyltin dichloride (DBT) and tributyltin chloride (TBT) inhibited 17beta-estradiol-induced cell proliferation at specific concentrations (500 nM and 10 nM, respectively).
- DBT and TBT also reduced testosterone-induced cell proliferation; TBT's effect was concentration-dependent on testosterone.
Conclusions:
- Butyltin compounds do not inhibit aromatase, suggesting this is not the mechanism for endocrine effects.
- DBT and TBT inhibit cell proliferation independently of the estrogen receptor, at non-cytotoxic concentrations.
- These compounds exhibit a functional anti-estrogenic response rather than acting as classical endocrine disruptors.
