Vitamin D: potential in the prevention and treatment of lung cancer.

Vitamin D is a steroid hormone traditionally recognized for maintaining calcium and phosphorous homeostasis in the body. However, it is now widely accepted that it exerts several extraskeletal actions, including anti- tumorigenic and immunomodulatory effects in vitro and in vivo. There is now a huge interest in studying the modes of action of vitamin D in a wide range of infectious and chronic disease settings and its potential in cancer prevention and treatment is currently under detailed investigation. In relation to the lung, evidence from observational studies, animal models and in vitro cell culture suggest that vitamin D may play a beneficial role in pulmonary inflammation. In addition, an adequate vitamin D status may be important for lung cancer prevention. Furthermore, vitamin D or its analogs, alone or in combination with cytotoxics, have potential in the treatment of lung cancer. Vitamin D is converted to its active form locally in the lung, suggesting that it may play an important role in lung health. Here, we review the evidence from observational, clinical and experimental studies in relation to vitamin D and lung cancer. In addition, we discuss vitamin D resistance in lung tumors and the potential molecular mechanisms of vitamin D action in lung cancer cells. Vitamin D is unique among vitamins, as it can be synthesized in the body as long as there is adequate sun exposure. The precursor of vitamin D 3 (cholecalciferol) is produced from the action of UVB radiation of 7-dehydrocholesterol within the skin. Limited amounts can also be obtained from the diet, with the richest sources in oily fish and fish oils. In plants and yeast, vitamin D 2 (ergocalciferol) is produced from irradiation of ergosterol. Vitamin D precursors (D indicating D 2 and D 3 ) are transported to the liver bound to the vitamin D-binding protein