Unità di Farmacologia e Tossicologia - Dipatimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli "Federico II", Naples, Italy.
Unità di Farmacologia Sperimentale - Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
Metabolomics. 2018 Feb 14;14(3):33. doi: 10.1007/s11306-018-1330-3.
Zearalenone (ZEN) is one of the most widely distributed toxins that contaminates many crops and foods. Its major metabolites are α-Zearalenol (α-zol) and β-Zearalenol. Previous studies showed that ZEN and α-zol have estrogenic properties and are able to induce growth promoting effect in breast tissues.
Considering that tumorigenesis is dependent on the reprogramming of cellular metabolism and that the evaluation of the cellular metabolome is useful to understand the metabolic changes that can occur during the cancer development and progression or after treatments, aim of our work is to study, for the first time, the effects of α-zol on the metabolomic profile of an estrogen positive breast cancer cell line, MCF-7, and of an estrogen negative breast cancer cell lines MDA-MB231.
Firstly, we tested the effects of α-zol on the cell viability after 24, 48 and 72 h of treatments with 10, 10 and 10 M concentrations on breast cancer MCF-7 and MDA-MB231 cell lines in comparison to human non-cancerous breast MCF10A cell line. Then, we evaluated cell cycle progression, levels of reactive oxygen species (ROS) and the metabolomic profiling by H-NMR approach on MCF-7 and MDA-MB231 before and after 72 h treatments. Principal component analysis was used to compare the obtained spectra.
α-zol is resulted able to induce: (i) an increase of the cell viability on MCF-7 cells mainly after 72 h treatment, (ii) a slight decrease of the cell viability on MDA-MB231 cells, and (iii) an increase of cells in S phase of the cell cycle and of ROS only in MCF-7 cells. Moreover, the evaluation of metabolomics profile evidenced that after treatment with α-zol the levels of some metabolites increased in MCF-7 cells whereas decreased slightly in MDA-MB231 cells.
Our results showed that α-zol was able to increase the protein biosynthesis as well as the lipid metabolism in MCF-7 cells, and, hence, to induce an estrogen positive breast cancer progression.
玉米赤霉烯酮（ZEN）是一种分布最广泛的毒素，污染了许多农作物和食品。它的主要代谢物是α-玉米赤霉醇（α-zol）和β-玉米赤霉醇。以前的研究表明，ZEN 和 α-zol 具有雌激素特性，并能够在乳腺组织中诱导生长促进作用。
考虑到肿瘤的发生依赖于细胞代谢的重编程，并且细胞代谢组学的评估有助于了解癌症发展和进展过程中或治疗后可能发生的代谢变化，我们的工作旨在首次研究 α-zol 对雌激素阳性乳腺癌细胞系 MCF-7 和雌激素阴性乳腺癌细胞系 MDA-MB231 的代谢组学谱的影响。
首先，我们测试了 10、10 和 10 M 浓度的 α-zol 在 MCF-7 和 MDA-MB231 乳腺癌细胞系中分别作用 24、48 和 72 小时后对细胞活力的影响，与非癌性乳腺 MCF10A 细胞系进行比较。然后，我们评估了细胞周期进程、活性氧（ROS）水平以及 MCF-7 和 MDA-MB231 在 72 小时处理前后的 H-NMR 方法的代谢组学谱。主成分分析用于比较获得的光谱。
α-zol 能够诱导：（i）MCF-7 细胞的细胞活力增加，主要是在 72 小时处理后，（ii）MDA-MB231 细胞的细胞活力略有下降，以及（iii）细胞周期 S 期的细胞数量增加和 ROS 仅在 MCF-7 细胞中增加。此外，代谢组学谱的评估表明，α-zol 处理后 MCF-7 细胞中的一些代谢物水平升高，而 MDA-MB231 细胞中的水平略有下降。
我们的结果表明，α-zol 能够增加 MCF-7 细胞中的蛋白质生物合成和脂质代谢，从而诱导雌激素阳性乳腺癌的进展。
