Abstract
Mercury remains a major environmental contaminant world-wide. Increasing evidence supports heavy metals as estrogenic agents (metalloestrogens), yet the impact of organic and inorganic mercury is unclear. The intent of this study was to increase understanding of mercury compounds as tumor causing agents and their modes of action. Changes in cellular viability, proliferation, and apoptosis after exposure to inorganic (HgCl2) and organic (CH3Hg+) mercury, were examined using a control human breast epithelial cell line (MCF-12A) compared to the human breast cancer cell lines, MCF-7 (ER+) and MDA-MB-453 (ER-). Exposure to mercuric compounds increased cellular proliferation (2-fold), altered caspase activity and p53 expression in a compound dependent manner in MCF-12A cells. Between the two tumor lines, MDA-MB-453 cells appeared most like MCF-12A cells with regard to the mercury response. MCF-7 (ER+) cells on the other hand, were relatively resistant to the effect of both HgCl2 and CH3Hg+ as indicated by the relative lack of change in any of the parameters measured. The proliferation and viability of MCF-7 cells was not significantly affected and although 5 ppm CH3Hg+ significantly increased caspase activity, there was a net inhibition of p53 expression at the same concentration. Collectively, MCF-12A (normal epithelial) cells were most sensitive to both HgCl2 and CH3Hg+. Cellular adaption and activation of the p53/apoptosis pathway would minimize tumorigenesis which was dependent on the chemical form of mercury. These protective effects were not observed in the tumor cell lines with the MCF-7 (ER+) cells being the most resistant to the mercury effects. A significant difference between MCF-7 and MDA-MB-453 cells is expression of the estrogen receptor, suggesting potential involvement of this receptor in the effects of mercuric compounds. Further work is necessary to examine the potential role of the estrogen receptor in modulating the effects of mercuric compounds on tumor development.
Highlights
Heavy metals such as cadmium, cobalt and lead among others are considered to be “metalloestrogens”, which interfere with, or disrupt, the estrogen system and its subsequent cellular pathways
One control that is frequently overlooked has been the ability of toxins such as heavy metals to interact directly with enzyme marker systems
We have shown that neither organic nor inorganic mercury interfere with caspase 3 or 7 activity and only a slight effect on purified Lactate Dehydrogenase (LDH) activity was observed
Summary
Heavy metals such as cadmium, cobalt and lead among others are considered to be “metalloestrogens”, which interfere with, or disrupt, the estrogen system and its subsequent cellular pathways. There has been a growing interest in these metalloestrogens and their role in estrogen-dependent breast cancers [2,3]. There has been little research exploring the potential of mercury as a metalloestrogen and its effect on estrogen receptor mediated pathways. The compound does not have to directly influence the functioning of estrogen receptors; instead, it may affect one or more steps in the estrogen-response cascade [6]. For those reasons we have chosen to examine inorganic and organic mercury effects on breast cancer cell line growth. The lines consist of a control epithelial line, an ER+ line and an ER- line
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
