MedWire News: Calcitriol, the active form of vitamin D, has been found to induce the tumor-suppressing protein CCAAT enhancer-binding protein (C/EBP)α, which can inhibit the growth of breast cancer cells, researchers report.
Low doses of the active form of vitamin D and non-steroidal anti-inflammatory drugs act as a powerful combination to halt the growth of prostate cancer cells, say US scientists.
Writing in Cancer Research, a team from Stanford University says it discovered that the amount of both activated vitamin D, or calcitriol, and NSAIDs could be reduced by half to one-tenth the dosage to thwart prostate cancer cell growth in cell lines and primary tissue culture
Elevated levels of the inflammatory marker C-reactive protein (CRP) are associated with an increased risk of death in men with advanced prostate cancer, according to findings from a subanalysis of the ASCENT (AIPC Study of Calcitriol Enhancing Taxotere) t
Vitamin D's days of obscurity seem pretty much over. Once just an afterthought to most people-relegated to the sides of milk cartons and the pages of medical texts-it's now on the cusp of becoming a full-fledged disease prevention star. Although vitamin D has long been known as an important factor in bone health, a quickly growing body of evidence now shows that it may also help lower the risk of cancer, heart disease, and even premature death.[1], [2] Not surprisingly, scientists and the public have started to take note, particularly of vitamin D's potential to protect against cancer
Holick MF.
Vitamin D: its role in cancer prevention and treatment.
Prog Biophys Mol Biol. 2006 Sep;92(1):49-59. Epub 2006 Mar 10. Review.
PMID: 16566961 [PubMed - indexed for MEDLINE]
Zittermann A.
Vitamin D in preventive medicine: are we ignoring the evidence?
Br J Nutr. 2003 May;89(5):552-72. Review.
PMID: 12720576 [PubMed - indexed for MEDLINE]
ScienceDaily (Sep. 1, 2005) - STANFORD, Calif. - The growth of prostate cancer cells can be halted by combining a form of vitamin D, available only by prescription, with low doses of an over-the-counter painkiller, researchers at the Stanford University School of Medicine have found. The combination reduced prostate cancer cell growth in a laboratory dish by up to 70 percent, according to the findings, published in the Sept. 1 issue of Cancer Research.
Li H, Stampfer MJ, Hollis JBW, Mucci LA, Gaziano JM, et al. (2007)
A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer.
PLoS Med 4(3): e103
doi:10.1371/journal.pmed.0040103
Evidence from clinical trials shows, with a wide margin of confidence, that a prolonged intake of 10,000IU/d of vitamin D3 poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D.
Vitamin D and cancer mini-symposium: the risk of additional vitamin D.
Vieth R.\nAnn Epidemiol. 2009 Jul;19(7):441-5. Epub 2009 Apr 11.
PMID: 19364661
doi:10.1016/j.annepidem.2009.01.009
Vitamin D and intervention trials in prostate cancer: from theory to therapy.
Schwartz GG.
Ann Epidemiol. 2009 Feb;19(2):96-102. Epub 2008 Jul 10.
PMID: 18619854
doi:10.1016/j.annepidem.2008.03.007
This suggests that whereas vitamin D (e.g., cholecalciferol) might prevent prostate cancer, existing prostate tumors likely would require treatment with 1,25(OH)(2)D and/or its analogs. The major obstacle to the use of 1,25(OH)(2)D in patients therapeutically is the risk of hypercalcemia. Several maneuvers to reduce this risk, including pulse dosing and the use of less calcemic 1,25(OH)(2)D analogs, have been explored in Phase I-III clinical trials. Once merely a promise, vitamin D-based therapies for prostate cancer may soon be medical practice.
Review article: vitamin D acquisition and breast cancer risk.
Pérez-López FR, Chedraui P, Haya J.
Reprod Sci. 2009 Jan;16(1):7-19. Review.
PMID: 19144887
DOI: 10.1177/1933719108327595
Conclusions: Although there are controversial results, it seems plausible that sufficient endogenous vitamin D levels may have a protective function on mammary cells, reducing breast cancer risk.
Epidemiology of vitamin D insufficiency and cancer mortality.
Pilz S, Tomaschitz A, Obermayer-Pietsch B, Dobnig H, Pieber TR.
Anticancer Res. 2009 Sep;29(9):3699-704. Review.
PMID: 19667167
In conclusion, we still need further studies to evaluate the association of vitamin D insufficiency and cancer incidence and mortality, but the multiple health benefits of vitamin D and the easy, safe and inexpensive way by which vitamin D can be supplemented should already guide current public health strategies to achieve 25(OH)D levels of at least 75 nmol/l (30 ng/ml) in the general population.
Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase.
Jiang F, Bao J, Li P, Nicosia SV, Bai W.
J Biol Chem. 2004 Dec 17;279(51):53213-21. Epub 2004 Oct 12.
PMID: 15485861
doi: 10.1074/jbc.M410395200
Overall, the study suggests that the down-regulation of telomerase activity by 1,25(OH)2VD3 and the resulting cell death are important components of the response of OCa cells to 1,25(OH)2VD3-induced growth suppression.
Progressive shortening of telomere associated with cell divisions limits the life span of normal cells and eventually leads to senescence. To become immortal, human cancers including OCa are invariably associated with activation of mechanism that maintains telomere length. Approximately 85-90% of cancers show reactivation of telomerase. The present study shows that telomerase in OCa cells is down-regulated by 1,25(OH)2VD3. Down-regulation of telomerase is due to decreased stability of hTERT mRNA rather than VDRE-mediated transcriptional repression through the putative VDRE present in the regulatory region of the hTERT gene.
It is known that the inhibition of telomerase may lead to a phenotypic lag during which cells would continue to divide until the point at which the telomeres became critically short. This phenomenon may explain why the apoptotic induction by 1,25(OH)2VD3 needs the treatment for more than 6 days. As mentioned in the results, no detectable shortening of telomeric repeats was observed in parental OVCAR3 cells after 9 days of treatment with 1,25(OH)2VD3 (Fig. 4D). This is likely due to the fact that the short telomere (about 3 kb) in OVCAR3 cells is very close to the minimal length required for survival and that cells with detectably shorter telomere may have been selected against apoptosis. It has been shown that transformed human cells enter crisis once the terminal restriction fragment of the telomere reaches a length of about 4 kb. This is insufficient to protect chro