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  • Title: Growth inhibition and differentiation in human prostate carcinoma cells induced by the vitamin D analog 1alpha,24-dihydroxyvitamin D2.
    Author: Bauer JA, Thompson TA, Church DR, Ariazi EA, Wilding G.
    Journal: Prostate; 2003 May 15; 55(3):159-67. PubMed ID: 12692781.
    Abstract:
    BACKGROUND: Vitamin D has been suggested as a chemopreventive and therapeutic modality for prostate cancer. However, hypercalcemic toxicity has limited the use of 1alpha,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) in clinical trials, prompting the search for analogs of vitamin D with less toxicity while retaining efficacy as a modality for cancer intervention. In this study, the less hypercalcemic vitamin D analog 1alpha,24-dihydroxyvitamin D(2) (1,24-(OH)(2)D(2)) was examined for its effects on cellular growth inhibition and differentiation induction in the LNCaP human prostate carcinoma cell line. METHODS: LNCaP cell growth was determined by quantifying DNA levels. Protein levels were determined using the ELISA method and immunoblotting. Levels of mRNA were determined using real-time quantitative reverse transcriptase PCR. RESULTS: LNCaP growth was decreased 50% by exposure to 0.01 nM 1,24-(OH)(2)D(2) after 96 hr in the presence of a growth stimulatory 0.1 nM dose of the androgen R1881. Prostate specific antigen (PSA) levels were increased 3.5-fold with 10 nM 1,24-(OH)(2)D(2) treatment compared to a 1.9-fold increase in PSA levels found with 10 nM 1,25-(OH)(2)D(3) under low androgen conditions. Neither 1,24-(OH)(2)D(2) nor 1,25-(OH)(2)D(3) affected the expression of cytokeratin 18 protein levels. Treatment with 10 nM 1,24-(OH)(2)D(2) alone produced a 1.3-fold increase in AR mRNA and a 2.2-fold increase in AR protein levels after 96 hr. Surprisingly, the addition of 1.0 nM R1881 alone or in combination with 10 nM 1,24-(OH)(2)D(2) produced an approximately 60% decrease in AR mRNA, whereas AR protein levels were increased 1.6-fold. CONCLUSIONS: Overall, 1,24-(OH)(2)D(2) was found to be at least as effective as 1,25-(OH)(2)D(3) at inhibiting growth and inducing differentiation markers in LNCaP prostate carcinoma cells and may thus prove useful in prostate cancer treatment.
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