College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.
Center for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Toxins (Basel). 2021 Jan 18;13(1):67. doi: 10.3390/toxins13010067.
The trophoblast, an embryonic tissue, exerts a crucial role in the processes of implantation and placentation. Toxins in food can cause malfunction of trophoblasts, resulting in apoptosis, oxidative stress, and abnormal angiogenesis. α-solanine, a steroidal glycoalkaloid, has antitumor properties on several cancer cells. However, its effect on human trophoblasts has not been elucidated. In this study, human extravillous trophoblast HTR-8/SVneo cells were exposed to α-solanine. Cellular functions including proliferation, migration, invasion, tube formation, and apoptosis were assessed. To monitor autophagic flux, trophoblasts were transfected with a mCherry-GFP-LC3B vector using lentiviral transduction, and expression of autophagy-related biomarkers including Beclin 1, Atgl3, and microtubule-associated protein 1 light chain-3 (MAP1-LC3) were detected. The results show that application of 20 μM α-solanine or above inhibited the cell viability, migration, invasion, and tube formation of the human trophoblast. Cell cycle was arrested at S and G2/M phases in response to 30 μM α-solanine. α-solanine induced apoptosis of HTR-8/SVneo cells and triggered autophagy by increasing the autophagic gene expression and stimulating the formation of autophagosome and autophagic flux. In conclusion, α-solanine can impair the functions of human trophoblast cells via activation of cell apoptosis and autophagy.
滋养层是一种胚胎组织,在着床和胎盘形成过程中发挥着关键作用。食物中的毒素会导致滋养层功能障碍,引发细胞凋亡、氧化应激和异常血管生成。α-茄碱是一种甾体糖苷生物碱,对多种癌细胞具有抗肿瘤作用。然而,其对人滋养层的影响尚未阐明。在这项研究中,人绒毛外滋养层 HTR-8/SVneo 细胞暴露于α-茄碱中。评估了细胞增殖、迁移、侵袭、管形成和细胞凋亡等功能。为了监测自噬流,用慢病毒转导将 mCherry-GFP-LC3B 载体转染滋养层,并检测自噬相关生物标志物包括 Beclin 1、Atgl3 和微管相关蛋白 1 轻链 3(MAP1-LC3)的表达。结果表明,应用 20μM 或更高浓度的α-茄碱抑制了人滋养层的细胞活力、迁移、侵袭和管形成。30μMα-茄碱使细胞周期停滞在 S 和 G2/M 期。α-茄碱通过增加自噬基因表达和刺激自噬体和自噬流的形成,诱导 HTR-8/SVneo 细胞凋亡并触发自噬。总之,α-茄碱可以通过激活细胞凋亡和自噬来损害人滋养层细胞的功能。