Prostate cancer angiogenesis declines after vitamin D suppresses interleukin-8


Prostate cancer angiogenesis declines after vitamin D suppresses interleukin-8.

"Angiogenesis is an essential step in initial tumor development and metastasis. Consequently, compounds that inhibit angiogenesis would be useful in treating cancer," scientists in the United States reported.

"A variety of antitumor effects mediated by 1 alpha, 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," wrote B.Y. Bao and colleagues, University of Rochester.

According to researchers, "Mechanistic dissection found that 1,25-VD inhibits NF-kappa B signal, one of the most important IL-8 upstream regulators. The 1,25-VD-mediated NF-kappa B signal reduction was shown to result from the blocking of nuclear translocation of p65, a subunit of the NF-kappa B complex, and was followed by attenuation of the NF-kappa B 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."

Researchers concluded, "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."

Bao and colleagues published their study in Carcinogenesis (1 alpha, 25-dihydroxyvitamin D-3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis. Carcinogenesis, 2006;27(9):1883-1893).

For more information, contact Y.F. Lee, University of Rochester, Medical Center, Dept. of Urology, 601 Elmwood Avenue, Box 656, Rochester, NY 14642, USA.

Publisher contact information for the journal Carcinogenesis is: Oxford University Press, Great Clarendon St., Oxford OX2 6DP, England.