Department of Toxicology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Molecules. 2023 Mar 18;28(6):2752. doi: 10.3390/molecules28062752.
The number of factors initiating and stimulating the progression of breast cancer are constantly increasing. Estrogens are a risk factor for breast adenocarcinoma, the toxicity of which increases as a result of metabolism and interaction with other factors. Due to the presence of environmental exposure to estrogens and metalloestrogens, we investigated how interactions between estrogens and toxic chromium(VI)[Cr(VI)] affect breast cancer lines and investigated whether estrogens play a protective role. The aim of the study was to investigate the effect of 17β-estradiol and its metabolites: 2-methoxyestradiol (2-MeOE2), 4-hydroxyestradiol (4-OHE2), and 16α-hydroxyestrone (16α-OHE1) in exposure to Cr(VI) on cell viability and DNA cell damage. Two estrogen-dependent breast cancer cell lines, MCF 7/WT and MDA-MB-175-VII, were examined. In addition, the expression of Cu-Zn superoxide dismutase (SOD1) was determined immunocytochemically to elucidate the mechanism of oxidative stress. The effects of single substances and their mixtures were tested in the model of simultaneous and 7-day estrogen pre-incubation. As a result, the viability of MCF-7 and MDA-MB-175-VII cells is lowered most by Cr(VI) and least by 17β-E2. In the combined action of estrogens and metalloestrogens, we observed a protective effect mainly of 17β-E2 against Cr(VI)-induced cytotoxicity. The highest expression of SOD1 was found in MCF-7/WT cells exposed to 17β-E2. Moreover, high apoptosis was caused by both Cr(VI) itself and its interaction with 4-OHE2 and 2-MeOE2. The direction and dynamics of changes in viability are consistent for both lines.
引发和刺激乳腺癌进展的因素数量不断增加。雌激素是乳腺腺癌的一个风险因素,其毒性因代谢和与其他因素的相互作用而增加。由于存在环境暴露于雌激素和金属雌激素,我们研究了雌激素与有毒铬(VI)[Cr(VI)]之间的相互作用如何影响乳腺癌细胞系,并研究了雌激素是否发挥保护作用。本研究旨在研究 17β-雌二醇及其代谢物:2-甲氧基雌二醇(2-MeOE2)、4-羟基雌二醇(4-OHE2)和 16α-羟雌酮(16α-OHE1)在暴露于 Cr(VI) 时对细胞活力和 DNA 细胞损伤的影响。检查了两种雌激素依赖性乳腺癌细胞系 MCF 7/WT 和 MDA-MB-175-VII。此外,通过免疫细胞化学测定铜锌超氧化物歧化酶(SOD1)的表达,阐明了氧化应激的机制。在同时和 7 天雌激素预孵育模型中测试了单一物质及其混合物的作用。结果,Cr(VI)对 MCF-7 和 MDA-MB-175-VII 细胞的活力降低最大,而 17β-E2 降低最小。在雌激素和金属雌激素的联合作用下,我们观察到主要由 17β-E2 对 Cr(VI)诱导的细胞毒性具有保护作用。在暴露于 17β-E2 的 MCF-7/WT 细胞中发现 SOD1 的表达最高。此外,Cr(VI)本身及其与 4-OHE2 和 2-MeOE2 的相互作用均导致高细胞凋亡。两种细胞系的活力变化方向和动态都是一致的。