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.