Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria 0083, Gauteng, South Africa.
National Health Laboratory Service, Tshwane Academic Division, Pretoria 0083, South Africa.
Int J Mol Sci. 2020 Dec 6;21(23):9296. doi: 10.3390/ijms21239296.
Vitamin D is a steroid hormone crucial for bone mineral metabolism. In addition, vitamin D has pleiotropic actions in the body, including anti-cancer actions. These anti-cancer properties observed within in vitro studies frequently report the reduction of cell proliferation by interruption of the cell cycle by the direct alteration of cell cycle regulators which induce cell cycle arrest. The most recurrent reported mode of cell cycle arrest by vitamin D is at the G1/G0 phase of the cell cycle. This arrest is mediated by p21 and p27 upregulation, which results in suppression of cyclin D and E activity which leads to G1/G0 arrest. In addition, vitamin D treatments within in vitro cell lines have observed a reduced C-MYC expression and increased retinoblastoma protein levels that also result in G1/G0 arrest. In contrast, G2/M arrest is reported rarely within in vitro studies, and the mechanisms of this arrest are poorly described. Although the relationship of epigenetics on vitamin D metabolism is acknowledged, studies exploring a direct relationship to cell cycle perturbation is limited. In this review, we examine in vitro evidence of vitamin D and vitamin D metabolites directly influencing cell cycle regulators and inducing cell cycle arrest in cancer cell lines.
维生素 D 是一种类固醇激素，对骨骼矿物质代谢至关重要。此外，维生素 D 在体内具有多种作用，包括抗癌作用。这些在体外研究中观察到的抗癌特性经常报告通过直接改变细胞周期调节剂来中断细胞周期，从而减少细胞增殖，从而诱导细胞周期停滞。维生素 D 最常报道的细胞周期阻滞模式是在细胞周期的 G1/G0 期。这种阻滞是通过 p21 和 p27 的上调介导的，导致细胞周期蛋白 D 和 E 的活性受到抑制，从而导致 G1/G0 阻滞。此外，在体外细胞系中观察到维生素 D 处理会降低 C-MYC 表达并增加视网膜母细胞瘤蛋白水平，这也导致 G1/G0 阻滞。相反，在体外研究中很少报道 G2/M 阻滞，并且这种阻滞的机制描述得很差。尽管已经认识到表观遗传学与维生素 D 代谢之间的关系，但探索与细胞周期干扰直接相关的研究有限。在这篇综述中，我们检查了维生素 D 和维生素 D 代谢物直接影响细胞周期调节剂并在癌细胞系中诱导细胞周期停滞的体外证据。
