Life Extension Update
Vitamin D antimetastasis mechanism reported
The January 2006 issue of the journal Carcinogenesis reported the findings of researchers at the University of Rochester Medical Center that vitamin D helps prevent the spread of prostate cancer cells by limiting the activity of two enzymes. Prior research has shown that vitamin D suppresses cancer progression, but its mechanisms were unclear. "We wanted to know the targets of vitamin D so we would know which patients would respond better," explained lead researcher and University of Rochester assistant professor of Urology Yi-Fen Lee, PhD.
Dr Lee and colleagues studied the effect of 1,25-hydroxyvitamin D3, the active form of vitamin D in the body, on three different prostate cancer cell lines. They examined three groups of proteases (enzymes that break down protein) involved in tumor invasion: the matrix metalloproteinases, the plasminogen activators, and the cathepsins. They found that treatment with vitamin D decreased the activity of matrix metalloproteinase-9 and the cathepsins, but not the plasminogen activators. Simultaneously, tissue inhibitors of metalloproteinase-1 (TIMP-1) and cathepsin inhibitors were found to have an increase in their activity.
The finding will prove particularly useful for individuals who have high levels of matrix metalloproteinase-9 and cathepsin activity. "Each individual is different so the therapy could be custom made for each person," Dr Lee remarked.
Dr Lee is currently investigating whether pharmaceutical agents or other vitamins, such as vitamin E, could enhance the anticancer benefits of vitamin D. She stated, "The best way to get vitamin D is to drink milk, get modest exposure to the sun, and take a vitamin pill to enrich the vitamin D, which might prevent cancer."
Genistein has been proposed as an effective agent to prevent the expression of metastatic capacity in hormone dependent cancers. In a cell-culture system, genistein appeared to be cytotoxic and inhibitory of PC cell proliferation (Geller et al., Prostate, 1998). Genistein and soy products therefore play a potential major role in established PC. Cancer cells use the enzyme tyrosine kinase as a growth factor. Soy genistein is a potent inhibitor of tyrosine kinase activity. The effects of protein kinase inhibitors on human prostate cell growth have been extensively investigated.
Other adjunctive therapies known to have an effect on PC include the use of vitamin D. Published studies using more potent synthetic vitamin D analogs such as Rocaltrol or Calcitriol have shown a slowing effect on PC growth (Gross et al., J. Urol., 1998). These analogs affect the p27Kip1 oncogene that results in over-expression of enzymes that inhibit part of the tumor cell cycle (Koike et al., Proc. Annu. Meet. Am. Assoc. Cancer Res., 1997). In short, synthetic vitamin D analogs cause a G1 arrest in the cell cycle by over-expression of cyclin-dependent kinase inhibitors (CDKIs).
The inhibition of new blood vessel formation to block the growth and spread of PC is currently under investigation. Androgen deprivation therapy (ADT) is known to have this antiangiogenesis effect as well as genistein. Other agents that have an effect on cancer cell invasiveness include green tea polyphenols. Green and black tea are derived from the same plant, Camellia sinensis. However, only green tea is rich in the flavonol group of polyphenols known as catechins. The fermentation process used in making black tea destroys the biologically active polyphenols of the fresh leaf. The catechins as a group have significant free radical scavenging ability and are potent antioxidants. Four catechins are found in green tea leaves:
Of these four factions EGCG is the most important to the PC patient.
The February 13, 2006 issue of the British Journal of Cancer reported the findings of researchers at Georgetown University 's Lombardi Comprehensive Cancer Center that genistein and indole-3-carbinol, found in soy and cruciferous vegetables such as broccoli, enhance DNA repair. The finding could explain, in part, the protective effect these compounds have been shown to provide against some cancers.
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