Vitamin D effects on differentiation and cell cycle

Differentiation can be considered to be, in essence, a persistent pattern of expression of previously dormant genes, which results in new functional capabilities of the differentiated cell. The new functions require cellular resources that compete with and finally titrate out the resources required for proliferation, and allow an accumulation of negative regulators of the cell cycle, which then predominate over the positive regulators. Thus, there is a reciprocal relationship between cellular differentiation and cell cycle progression/proliferation, though there is also evidence that differentiation and cycle arrest need not be strictly coupled. Cell cycle changes in differentiating cells need not take place immediately-in some cells there is at first a boost of proliferation-as in normal hematopoiesis, or in HL60 and U937 cells differentiating in response to derivatives of vitamin D₃. However, even in these cases, there is an eventual slowdown of the cell cycle traverse and cessation of proliferation of differentiated cells. Consequently, numerous attempts are being made to exploit the differentiating actions of vitamin D and its analogs to induce proliferative quiescence of neoplastic cells, and thus increase the range of options for optimal therapy of human cancer.