Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells

Abstract

Abstract. Neuroblastoma (NB) is the most common pediatric extracranial cancer. Metastasis is the main cause of mortality in NB patients. Currently, little is known about the risk factors and their mechanisms that cause metastasis. Environmental endocrine disruptors (EED) are recently identified risk factors associated with various human diseases including malignant tumors. Our previous studies have implicated the role of di(2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA), two of the most common EED, in neuroblastoma cell proliferation. Here, we further investigated the effects of DEHP, BPA as well as 17ß-estradiol (E 2 ) on the invasion and metastasis of human neuroblastoma SK-N-SH cells in vitro. SK-N-SH cells expressed estrogen receptor (ER)-ß, matrix metalloproteinases-2 (MMP-2), MMP-9 and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) at readily detectable levels. 50 μM DEHP, 0.1 μM BPA and 10 μM E 2 exposure all resulted in enhanced motility and invasiveness of SK-N-SH cells (P<0.001), elevated expression of MMP-2 and MMP-9, and decreased expression of TIMP-2 (P<0.01). Furthermore, phosphorylation of Akt (Ser473) was also induced following the exposure (P<0.01). Importantly, both ER antagonist ICI182,780 and phosphoinositide 3-kinase (PI3K) specific inhibitor LY294002 significantly inhibited the DEHP, BPA, or E 2 -induced cell migration and invasion, as well as the disregulation of MMP-2, MMP-9 and TIMP-2 expression. ICI182,780 may have worked through abolishing Akt (Ser473) phosphorylation. In conclusion, DEHP, BPA, and E 2 potently promote invasion and metastasis of neuroblastoma cells through overexpression of MMP-2 and MMP-9 as well as downregulation of TIMP-2. ER-dependent pathway and PI3K/Akt pathway are involved, which may become potential therapeutic targets for neuroblastoma treatment.

Determination of Bisphenol a (BPA) migration in Şavak brine cheese stored in polyethylene terephthalate (PET) packaging by HPLC method

“…Bisphenols can accumulate in the adipose tissue of the animal, secreted in milk fat, and stored in fatty dairy products (Santonicola et al 2021). BPA has carcinogenic effects (Zhu et al 2010;Huang et al 2012;Derouiche et al 2013;Ptak et al 2014;Wang et al 2015;Castillo Sanchez et al 2016;Shi et al 2016) on human health, effects on the nervous system and behaviour (Ishido and Suzuki 2010;Nagao et al 2014), endocrine-disrupting effects, and allergic effects (Hong 2012;Pupo 2012;Chavdarova et al 2015). It has also been reported that it can cause problems such as diabetes, cardiovascular diseases, inflammations (Rubin 2011;Wang et al 2015;Han and Hong 2016), in addition to infertility, obesity, thyroid hormone disorders (Mili c et al 2015), and further complications including abortion, abnormal fetal karyotype, endometrial hyperplasia, and polycystic ovary syndrome (Takeuchi and Tsutsumi 2002;Yamada et al 2002;Sugiura-Ogasawara et al 2005;Vandenberg et al 2007;Wang et al 2015).…”