Worldsfirstnaturalproducts.com

The American Journal of Pathology, Vol. 173, No. 5, November 2008 Copyright American Society for Investigative Pathology Correspondence
Vitamin D May Reduce Prostate Cancer Metastasisby Several Mechanisms Including Blocking Stat3 calcitriol.12 Prostate cells express vitamin D-25-hydroxy-lase (25-OHase) and can convert calcidiol to calcitriol.13 The recent article by Abdulghani and colleagues1 in re- Thus, making sure that those diagnosed with prostate porting that Stat3 promotes metastatic progression of cancer have high calcidiol levels might be appropriate.
prostate cancer opens the door to new approaches to In conclusion, the findings by Abdulghani and col- fight this cancer. This letter proposes that vitamin D might leagues1 might help to explain the benefit of vitamin D in be beneficial in reducing the risk of prostate cancer increasing the survival rate for prostate cancer, and the mortality by inhibiting the action of Stat3.
findings by Muthian and colleagues9 might help lead to a Solar UVB and vitamin D have long been hypothesized therapeutic way to reduce the role of Stat3 in leading to to reduce the risk of prostate cancer mortality.2 Whereas solar UVB is correlated with increased survival for thosediagnosed with prostate cancer,3 serum 25-hydroxyvita- min D (calcidiol) measured 1 to 8 years before detection Sunlight, Nutrition, and Health Research Center of prostate cancer generally does not show a significant correlation with incidence, although higher calcidiol lev-els are significantly correlated with more aggressiveforms of prostate cancer.4 These findings suggest that vitamin D is more effective at reducing metastasis thanprogression of prostate cancer. Similar results have been 1. Abdulghani J, Gu L, Dagvadorj A, Lutz J, Leiby B, Bonuccelli G, found for many other cancers, based on the dependence Lisanti MP, Zellweger T, Alanen K, Mirtti T, Visakorpi T, Bubendorf L, of cancer survival on season in Norway5 and that solar Nevalainen MT: Stat3 promotes metastatic progression of prostate UVB is more highly correlated with cancer mortality rates cancer. Am J Pathol 2008, 172:1717–1728 2. Schwartz GG, Hulka BS: Is vitamin D deficiency a risk factor for than cancer incidence rates for many cancers in the prostate cancer? (Hypothesis). Anticancer Res 1990, 10:1307–1311 3. Lagunova Z, Porojnicu AC, Dahlback A, Berg JP, Beer TM, Moan J: Laboratory studies with the hormonal metabolite of Prostate cancer survival is dependent on season of diagnosis. Pros- vitamin D, 1,25-dihydroxyvitamin D (calcidiol), indicate 4. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, that calcidiol might be effective in combating prostate Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB: Prostate, cancer. One study found that calcitriol inhibits the syn- Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team: thesis and actions of pro-inflammatory prostaglandins by serum vitamin D concentration and prostate cancer risk: a nested three mechanisms.7 Another study identified calcitriol as case-control study. J Natl Cancer Inst 2008, 100:796 – 804 5. Porojnicu AC, Dahlback A, Moan J: Sun exposure and cancer survival a negative regulator of androgen inactivation in prostate in Norway: changes in the risk of death with season of diagnosis and cancer LNCaP cells.8 With respect to Stat3, it was re- latitude. Adv Exp Med Biol 2008, 624:43–54 ported that in vitro treatment of activated T cells with 6. Boscoe FP, Schymura MJ: Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002. BMC Can- calcidiol inhibited the interleukin-12-induced tyrosine phosphorylation of Stat3.9 Several studies have reported 7. Krishnan AV, Moreno J, Nonn L, Swami S, Peehl DM, Feldman D: that inhibiting phosphorylation of Stat3 impairs the role of Calcitriol as a chemopreventive and therapeutic agent in prostate Stat3 in carcinogenesis. In one study, decreased phos- cancer: role of anti-inflammatory activity. J Bone Miner Res 2007,22(Suppl 2):V74 –V80 phorylation decreased induction of Stat3 target genes 8. Kaeding J, Be´langer J, Caron P, Verreault M, Be´langer A, Barbier O: and increased apoptosis10; in another, decreased phos- Calcitrol (1alpha,25-dihydroxyvitamin D3) inhibits androgen glucu- phorylation decreased transforming growth factor-␤-me- ronidation in prostate cancer cells. Mol Cancer Ther 2008, 7:380 –390 diated invasion and metastasis in pancreatic cancer 9. Muthian G, Raikwar HP, Rajasingh J, Bright JJ: 1,25 Dihydroxyvita- To date the beneficial role of calcidiol in reducing the WBG receives funding from the UV Foundation (McLean, VA), the Vitamin risk of death from prostate cancer3 is stronger than that of D Society (Canada), and the European Sunlight Association.
AJP November 2008, Vol. 173, No. 5 min-D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis lead- Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM, Carducci ing to Th1 response in experimental allergic encephalomyelitis.
MA, Vicario D, Dreicer R, Higano CS, Ahmann FR, Chi KN, Henner WD, Arroyo A, Clow FW: ASCENT Investigators: double-blinded ran- 10. Herrmann A, Vogt M, Mo¨nnigmann M, Clahsen T, Sommer U, Haan S, domized study of high-dose calcitriol plus docetaxel compared with Poli V, Heinrich PC, Mu¨ller-Newen G: Nucleocytoplasmic shuttling of placebo plus docetaxel in androgen-independent prostate cancer: a persistently activated STAT3. J Cell Sci 2007, 120:3249 –3261 report from the ASCENT Investigators. J Clin Oncol 2007, 11. Zhao S, Venkatasubbarao K, Lazor JW, Sperry J, Jin C, Cao L, Freeman JW: Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses trans- 13. Flanagan JN, Young MV, Persons KS, Wang L, Mathieu JS, Whitlatch forming growth factor beta-mediated invasion and metastasis in pancreatic LW, Holick MF, Chen TC: Vitamin D metabolism in human prostate cancer cells. Cancer Res 2008, 68:4221–4228 cells: implications for prostate cancer chemoprevention by vitamin D.
12. Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD,

Source: http://worldsfirstnaturalproducts.com/relevantstudies/Vitamin_D3_Study_3.pdf