TY  - JOUR
T1  -  1α, 25-dihydroxyvitamin D 3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis 
AU  - Bao, Bo-Ying
AU  - Yao, Jorge
AU  - Lee, Yi-Fen
Y1  - 2006/09/01
N1  - 10.1093/carcin/bgl041
JO  - Carcinogenesis
SP  - 1883
EP  - 1893
VL  - 27
IS  - 9
N2  -  Angiogenesis is an essential step in initial tumor development and metastasis. Consequently, compounds that inhibit angiogenesis would be useful in treating cancer. A variety of antitumor effects mediated by 1α, 25-dihydroxyvitamin D 3 (1,25-VD) have been reported, one of which is anti-angiogenesis; however, detailed mechanisms remain unclear. We have demonstrated that 1,25-VD inhibits prostate cancer (PCa) cell-induced human umbilical vein endothelial cell migration and tube formation, two critical steps involved in the angiogenesis. An angiogenesis factor, interleukin-8 (IL-8), secreted from PCa cell was suppressed by 1,25-VD at both mRNA and protein levels. Mechanistic dissection found that 1,25-VD inhibits NF-κB signal, one of the most important IL-8 upstream regulators. The 1,25-VD-mediated NF-κB signal reduction was shown to result from the blocking of nuclear translocation of p65, a subunit of the NF-κB complex, and was followed by attenuation of the NF-κB complex binding to DNA. The role of IL-8 in PCa progression was further examined by PCa tissue microarray analyses. We found that IL-8 expression was elevated during PCa progression, which suggests that IL-8 may play a role in tumor progression mediated through its stimulation on angiogenesis. These findings indicate that 1,25-VD could prevent PCa progression by interrupting IL-8 signaling, which is required in tumor angiogenesis, and thus applying vitamin D in PCa treatment may be beneficial for controlling disease progression. 
SN  - 0143-3334
M3  - doi: 10.1093/carcin/bgl041
UR  - http://dx.doi.org/10.1093/carcin/bgl041
ER  -