Prostate cancer prevention by vitamin D studied

NewsRx.com

06-01-06

Decreased prostatic inflammation was suggested as a potential mechanism for prostate cancer prevention by 1,25-dihydroxyvitamin-D-3 (1,25D).

According to recent research published in the journal Cancer Research, "Although numerous studies have implicated vitamin D in preventing prostate cancer, the underlying mechanism(s) remains unclear. Using normal human prostatic epithelial cells, we examined the role of mitogen-activated protein kinase phosphatase 5 (MKP5) in mediating cancer preventive activities of vitamin D."

"Up-regulation of MKP5 mRNA by 1,25D was dependent on the vitamin D receptor. We also identified a putative positive vitamin D response element within the MKP5 promoter that associated with the vitamin D receptor following 1,25D treatment. MKP5 dephosphorylates/inactivates the stress-activated protein kinase p38," explained L. Nonn and colleagues, Stanford University.

"Treatment of prostate cells with 1,25D inhibited p38 phosphorylation, and MKP5 small interfering RNA blocked this effect. Activation of p38 and downstream production of interleukin 6 (IL-6) are proinflammatory. Inflammation and IL-6 overexpression have been implicated in the initiation and progression of prostate cancer. 1,25D pretreatment inhibited both UV- and tumor necrosis factor alpha-stimulated IL-6 production in normal cells via p38 inhibition.

"Consistent with inhibition of p38, 1,25D decreased UV-stimulated IL-6 mRNA stabilization. The ability of 1,25D to up-regulate MKP5 was maintained in primary prostatic adenocarcinoma cells but was absent in metastases-derived prostate cancer cell lines. The inability of 1,25D to regulate MKP5 in the metastasis-derived cancer cells suggests there may be selective pressure to eliminate key tumor suppressor functions of vitamin D during cancer progression," relayed the investigators.

The researchers concluded, "These studies reveal MKP5 as a mediator of p38 inactivation and decreased IL-6 expression by 1,25D in primary prostatic cultures of normal and adenocarcinoma cells, implicating decreased prostatic inflammation as a potential mechanism for prostate cancer prevention by 1,25D."

Nonn and colleagues published their study in Cancer Research (Inhibition of p38 by vitamin D reduces interleukin-6 production in normal prostate cells via mitogen-activated protein kinase phosphatase 5: Implications for prostate cancer prevention by vitamin D. Cancer Res, 2006;66(8):4516-4524).

For additional information, contact D.M. Peehl, Stanford University, Dept. Urology, Medical Center, School of Medicine, 300 Pasteur Dr., Stanford, CA 94305, USA.

The publisher's contact information for the journal Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17th Floor, Philadelphia, PA 19106-4404, USA.

Keywords: Stanford, California, United States, Diet and Nutrition, Men's Health, Oncology, Phosphatase, Prostate Cancer, Prostate Carcinoma, Tumor Suppression, Tumors, Vitamin D Receptors, Prostatic Inflammation, Mechanism, Prostate Cancer Prevention, 1,25-Dihydroxyvitamin-D-3. This article was prepared by Biotech Week editors from staff and other reports. Copyright 2006, Biotech Week via NewsRx.com.

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