Exploring vitamin D metabolism and function in cancer

Abstract

Vitamin D, traditionally known as an essential nutrient, is a precursor of a potent steroid hormone that regulates a broad spectrum of physiological processes. In addition to its classical roles in bone metabolism, epidemiological, preclinical, and cellular research during the last decades, it revealed that vitamin D may play a key role in the prevention and treatment of many extra-skeletal diseases such as cancer. Vitamin D, as a prohormone, undergoes two-step metabolism in liver and kidney to produce a biologically active metabolite, calcitriol, which binds to the vitamin D receptor (VDR) for the regulation of expression of diverse genes. In addition, recent studies have revealed that vitamin D can also be metabolized and activated through a CYP11A1-driven non-canonical metabolic pathway. Numerous anticancer properties of vitamin D have been proposed, with diverse effects on cancer development and progression. However, accumulating data suggest that the metabolism and functions of vitamin D are dysregulated in many types of cancer, conferring resistance to the antitumorigenic effects of vitamin D and thereby contributing to the development and progression of cancer. Thus, understanding dysregulated vitamin D metabolism and function in cancer will be critical for the development of promising new strategies for successful vitamin D-based cancer therapy.

Cancer: The significance of vitamin D metabolism

Altered vitamin D metabolism in cancer patients might help tumors progress, and understanding this effect could guide new anti-cancer therapies. Sang-Min Jeon and Eun-Ae Shin at Ajou University in South Korea review research on links between cancer and vitamin D metabolism. Vitamin D is best known for its role in building and maintaining healthy bones. Many epidemiological studies, however, suggest vitamin D deficiency is also involved in diseases affecting tissues other than bone. Sunlight promotes vitamin D formation, and low exposure to sunlight was found to be associated with increased incidence of cancer more than 80 years ago. Vitamin D deficiency has since been implicated in at least 18 types of cancer. The authors summarize the metabolic processes underlying the anti-cancer effects of vitamin D, and discuss ways to improve vitamin D-based therapies for cancer.