Vitamin D plus NSAIDs for prostate cancer

[Guest guest]

Vitamin D boosts NSAID cancer-fighting power

http://www.nutraingredients.com/news/ng.asp?n=62261 & m=1NIE902 & c=lqeudkujayvvlpc

02/09/2005- 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 cultures.

If work in animal models and human trials confirm the findings, the

combination may help to keep the NSAID family of drugs among the

pharmaceutical choices for the prevention and treatment of cancer, it

said.

Such drugs include ibuprofen, indomethacin and naproxen, as well as

the COX-2 inhibitors linked to increased risk for cardiovascular

disease, Vioxx and Celebrex.

" NSAIDs have their own risks, " said Feldman, professor of

Medicine at Stanford's division of Endocrinology, Gerontology and

Metabolism.

" So, we have to be careful even with lower doses and we still need to

watch the patients very closely if we intend to keep them on these

drugs for extended periods of time. But we are aiming to find doses

that are less toxic and far more tolerable for the patient. "

The scientists found that vitamin D works to limit the growth of

prostate cancer cells by interfering with the same molecules attacked

by NSAIDs - the prostaglandin/COX-2 pathway.

Prostaglandins are responsible for activating the inflammatory

response that results in pain and fever. NSAIDs work by blocking an

enzyme called cyclooxygenase-2 or COX-2 which is essential for

prostaglandin synthesis, thereby relieving some of the effects of pain

and fever.

In this study, activated vitamin D or calcitriol was shown to act as a

triple threat against this pathway, in prostate cancer cells.

First, it limits the expression of a key enzyme needed to synthesize

prostaglandins into COX-2. Then it increases the expression of an

enzyme that rapidly disassembles active prostaglandin molecules, thus

promoting the breakdown of the hormone.

Finally, the scientists discovered that calcitriol inhibits the

production of two cell receptors used by prostaglandins to regulate

gene expression and control tumor proliferation.

While the scientists showed that activated vitamin D, calcitriol,

works by itself to limit prostate cancer growth, it is equally

effective in much smaller doses when used in combination with NSAIDs.

Furthermore, calcitriol dramatically reduces the amount of NSAIDs

necessary to curb prostate cancer cell growth.

This is particularly important now, in light of recent studies showing

that some NSAIDs that are selective for COX-2 targeting, such as Vioxx

and Celebrex, are linked to cardiovascular disease at their prescribed

doses.

While their studies provide insight into cellular activities

controlled by both calcitriol and the NSAIDs, Feldman and his

colleagues remain cautious about advancing their new-found

understanding of prostaglandin chemistry into patients.

" We need to verify that vitamin D and NSAIDs work in synergy not just

in these cell lines, but also work in the same manner, in humans which

have a vastly more complex physiology than simple cells in a culture

plate, " Feldman said.

Vitamin D is converted in the liver and kidney to the active form

called calcitriol, a hormone that has widespread actions in the body.

Vitamin D available over the counter would not achieve the therapeutic

levels of calcitriol needed to inhibit cancer cell growth, since the

body has mechanisms to limit its activation to calcitriol, Feldman

explained.