Page 156 - Vitamin D and Cancer

Chapter 7
Induction of Differentiation in Cancer Cells
by Vitamin D: Recognition and Mechanisms *

Elzbieta Gocek and George P. Studzinski

Abstract Current understanding of the vitamin D-induced differentiation of neoplastic
cells, which results in the generation of cells that acquire near-normal, mature
phenotype is summarized here. The criteria by which differentiation is recognized in
each cell type are provided, and only those effects of 1a,25-dihydroxyvitamin D
3
(1,25D) on cell proliferation and survival which are associated with the differentia-
tion process are emphasized. The existing knowledge of the signaling pathways that
lead to vitamin-D-induced differentiation of colon, breast, prostate, squamous cell
carcinoma (SCC), osteosarcoma, and myeloid leukemia cancer cells is outlined.
Where known, the distinctions between the different mechanisms of 1,25D-induced
differentiation which are cell-type-specific and cell-context-specific are pointed
out. A considerable body of evidence suggests that several types of human cancer
cells can be suitable candidates for chemoprevention or differentiation therapy with
vitamin D. However, further studies of the underlying mechanisms are needed to
gain further insights on how to improve the therapeutic approaches that incorporate
vitamin D derivatives.

Abbreviations

A Androgen
AKT Serine/threonine-specific protein kinase B
Alk Pase Alkaline phosphatase
AML Acute myeloid leukemia
AP-1 Activating protein 1
APC Adenomatous polyposis coli
APL Acute promyelocytic leukemia

*The substance of this chapter has been reported as an Invited Review on the same topic in “Crit
Rev Clin Lab Sci.”
G.P. Studzinski (*)
Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School,
185 So. Orange Ave., Room 543, Newark, NJ 07101–1709, USA
e-mail: studzins@umdnj.edu

D.L. Trump and C.S. Johnson (eds.), Vitamin D and Cancer, 143
DOI 10.1007/978-1-4419-7188-3_7, © Springer Science+Business Media, LLC 2011