Carcinogenesis Advance Access published online on April 19, 2006
Carcinogenesis, doi:10.1093/carcin/bgl041
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1 Department of Urology, University of Rochester, Rochester, NY 14642, USA; Department of Chemical Engineering, University of Rochester, Rochester, NY 14642, USA
* To whom correspondence should be addressed. 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 anti-tumor effects mediated by 1
Received September 20, 2005
Revised March 22, 2006
Accepted March 31, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1
Bo-Ying Bao 1,
Jorge Yao 2,
and
Yi-Fen Lee 3 *
, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis
2 Department of Pathology, University of Rochester, Rochester, NY 14642, USA
3 Department of Urology, University of Rochester, Rochester, NY 14642, USA
Yi-Fen Lee, E-mail: yifen_lee{at}urmc.rochester.edu
Abstract 
, 25-dihydroxyvitamin D3 have been reported, one of which is anti-angiogenesis; however, detailed mechanisms remain unclear. We have demonstrated that 1, 25-dihydroxyvitamin D3 inhibits prostate cancer cell-induced human umbilical vein endothelial cell migration and tube formation, two critical steps involved in the angiogenesis. An angiogenesis factor, interleukin-8, secreted from prostate cancer cell was suppressed by 1, 25-dihydroxyvitamin D3 at both mRNA and protein levels. Mechanistic dissection found that 1, 25-dihydroxyvitamin D3 inhibits NF-
B signal, one of the most important interleukin-8 upstream regulators. The 1, 25-dihydroxyvitamin D3-mediated NF-B signal reduction was shown to result from the blocking of nuclear translocation of p65, a subunit of the NF-B complex, and was followed by attenuation of the NF-B complex binding to DNA. The role of interleukin-8 in prostate cancer progression was further examined by prostate cancer tissue microarray analyses. We found that interleukin-8 expression was elevated during prostate cancer progression, which suggests interleukin-8 may play a role in tumor progression mediated through its stimulation on angiogenesis. These findings indicate that 1, 25-dihydroxyvitamin D3 could prevent prostate cancer progression by interrupting interleukin-8 signaling, which is required in tumor angiogenesis, and thus applying vitamin D in the prostate cancer treatment may be beneficial for controlling disease progression.
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