Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy.
Section of Anatomic Pathology and Histology, Department of Medicine and Surgery, University of Perugia, 06126 Perugia, Italy.
Int J Mol Sci. 2023 Dec 8;24(24):17263. doi: 10.3390/ijms242417263.
The role of sphingomyelin metabolism and vitamin C in cancer has been widely described with conflicting results ranging from a total absence of effect to possible preventive and/or protective effects. The aim of this study was to establish the possible involvement of sphingomyelin metabolism in the changes induced by vitamin C in breast cancer cells. The MCF7 cell line reproducing luminal A breast cancer and the MDA-MB-231 cell line reproducing triple-negative breast cancer were used. Cell phenotype was tested by estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 expression, and proliferation index percentage. Sphingomyelin was localized by an EGFP-NT-Lys fluorescent probe. Sphingomyelin metabolism was analyzed by RT-PCR, Western blotting and UFLC-MS/MS. The results showed that a high dose of vitamin C produced reduced cell viability, modulated cell cycle related genes, and changed the cell phenotype with estrogen receptor downregulation in MCF7 cell. In these cells, the catabolism of sphingomyelin was promoted with a large increase in ceramide content. No changes in viability and molecular expression were observed in MB231 cells. In conclusion, a high dose of vitamin C induces changes in the luminal A cell line involving sphingomyelin metabolism.
鞘脂代谢和维生素 C 在癌症中的作用已经被广泛描述，结果相互矛盾，从完全没有影响到可能具有预防和/或保护作用。本研究的目的是确定鞘脂代谢是否参与了维生素 C 诱导的乳腺癌细胞的变化。使用了模拟腔 A 型乳腺癌的 MCF7 细胞系和模拟三阴性乳腺癌的 MDA-MB-231 细胞系。通过雌激素受体、孕激素受体、人表皮生长因子受体 2 的表达和增殖指数百分比来测试细胞表型。通过 EGFP-NT-Lys 荧光探针定位鞘磷脂。通过 RT-PCR、Western blot 和 UFLC-MS/MS 分析鞘脂代谢。结果表明，高剂量的维生素 C 降低了细胞活力，调节了与细胞周期相关的基因，并改变了 MCF7 细胞的细胞表型，使雌激素受体下调。在这些细胞中，鞘磷脂的分解代谢被促进，神经酰胺含量大量增加。MB231 细胞中未观察到活力和分子表达的变化。总之，高剂量的维生素 C 诱导腔 A 细胞系发生变化，涉及鞘脂代谢。
