The Influence of Interaction between Cadmium with 17β-Estradiol, 2-Methoxyestradiol and 16α-Hydroxyestrone on Viability and p-Glycoprotein in Ovarian Cancer Cell Line.

Ewa Sawicka,Julita Kulbacka,Martyna Szydełko,Beata Szymańska,Jolanta Saczko,Agnieszka Piwowar

doi:10.3390/ijms23052628

Ewa Sawicka, Julita Kulbacka + Show 4 more

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https://doi.org/10.3390/ijms23052628

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Abstract

Occupational and environmental exposure to xenoestrogens, a subgroup of endocrine disruptors (EDCs), can affect the endocrine system and increase the risk of cancer, primarily the hormone-dependent kind. This type of cancer includes ovarian cancer, which is the leading cause of death from gynecological tumors. The aim of this study was to assess the role of 17β-estradiol and its metabolites: 2-MeOE2, 16α-OHE1 in exposure to the metalloestrogen cadmium. The effect of interactions of cadmium with estrogens on the viability of cells in malignant ovarian cancer cells SKOV-3 was investigated, both in simultaneous action and in the pre-incubation model. There are no known interactions between estrogens and cadmium in ovarian cancer cells. Due to the frequent occurrence of multidrug resistance (MDR) in ovarian cancer, the effects of estrogens and cadmium on MDR in SKOV-3, measured as P-glycoprotein (P-gp), were assessed. An interaction study showed that E2 had an antagonistic effect on cadmium-induced cell damage, while 2-MeOE2 showed less of a protective effect in combination with CdCl2 than E2. There were two types of interaction: toxic synergism and beneficial antagonism. E2 and cadmium increased P-gp expression in SKOV-3 cells, while 2-MeOE2 decreased P-gp expression to a potentially beneficial effect on MDR prevention. The obtained results constitute an interesting starting point for further research in the field of interactions between estrogens and xenoestrogens in ovarian cancer.

Highlights

Cadmium is a highly toxic non-essential transition metal that constitutes an important potential health risk to the environment [1]
Since ovarian cancer is one of many cancers associated with multi-drug resistance, we studied the effects of estrogens and cadmium on glycoprotein expression
Compounds capable of affecting the human hormone balance by binding to the estrogen receptor are widespread in the environment

Summary

Introduction

Cadmium is a highly toxic non-essential transition metal that constitutes an important potential health risk to the environment [1]. Multiple mechanisms potentially relate cadmium to cancer; these include oxidative stress or inflammation, interference with DNA repair and changes of DNA methylation. More importantly in respect to hormone-related cancers, there is evidence that cadmium may act on estrogenic signaling pathways, resulting, among others, in the proliferation of breast cancer cells in vitro [2,3]. The literature data on the effect of cadmium on breast cancer are numerous, but there is little data on ovarian cancer (OCa). This study analyzes the available data from the Third National Health and Nutrition Examination Survey, which suggests a link between exposure to cadmium and increased mortality from ovarian cancer [4]. García-Perez et al [2015] revealed a statistically significant increase in the incidence of, and mortality from, ovarian cancer in the proximity of cadmium-emitting refineries [5]

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