Effects of vitamin D as a regulator of androgen intracrinology in LNCAP prostate cancer cells.

Prostate cancer is initially treated via androgen deprivation therapy (ADT), a highly successful treatment in the initial pursuit of tumor regression, but commonly restricted by the eventual emergence of a more lethal 'castrate resistant' form of the disease. Intracrine pathways that utilize dehydroepiandrosterone (DHEA) or other circulatory precursor steroids, are thought to generate relevant levels of growth-stimulating androgens such as testosterone (T) and dihydrotestosterone (DHT). In this study, we explored the capacity of the active vitamin D hormone to interact and elicit changes upon this prostatic intracrine pathway at a metabolic level.

Vitamin D receptor agonist EB1089 is a potent regulator of prostatic "intracrine" metabolism.

Background: A contributing factor to the emergence of castrate resistant prostate cancer (CRPC) is the ability of the tumor to circumvent low circulating levels of testosterone during androgen deprivation therapy (ADT), through the production of "intracrine" tumoral androgens from precursors including cholesterol and dehydroepiandrosterone (DHEA). As these processes promote AR signaling and prostate cancer progression their modulation is required for disease prevention and treatment.

Methods: We evaluated the involvement of the vitamin D receptor ligand EB1089 in the regulation of genes with a role in androgen metabolism using the androgen dependent cell lines LNCaP and LAPC-4.