Activated vitamin D and NSAIDs form one-two punch against prostate cancer cells

[Guest guest]

Colleagues, the following is FYI and does not necessarily reflect my own

opinion. I have no further knowledge of the topic.

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Public release date: 1-Sep-2005

http://www.eurekalert.org/pub_releases/2005-09/aafc-avd083005.php

Contact: Vanderboom, Ph.D.

vanderboom@...

American Association for Cancer Research

Activated vitamin D and NSAIDs form one-two punch against prostate

cancer cells

PHILADELPHIA – Low doses of the active form of vitamin D and

non-steroidal anti-inflammatory drugs, taken in combination, have been

shown to act as a powerful one-two punch that knocks down the growth of

prostate cancer cells.

In a study published in the journal " Cancer Research " , scientists from

Stanford University discovered that the amount of both -- activated

vitamin D, or calcitriol, and the 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 drug

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

pharmaceutical choices for the prevention and treatment of cancer. This

list includes ibuprofen, indomethacin and naproxen, in addition to other

so-called COX-2 inhibitors linked to increased risk for cardiovascular

disease, including Vioxx® and Celebrex®.

" NSAIDs have their own risks, " said Feldman, M.D., professor of

Medicine in the Division of Endocrinology, Gerontology and Metabolism at

the Stanford University School of Medicine. " 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. "

As outlined in their study, the Stanford scientists discovered that

vitamin D, known as the " sunshine vitamin, " 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.

# Second, it increases the expression of an enzyme that rapidly

disassembles active prostaglandin molecules, thus promoting the

breakdown of the hormone.

# Third, 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

rofecoxib (Vioxx®) and celecoxib (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. The

Feldman laboratory used calcitriol in the experiments reported in the

Cancer Research article. Vitamin D in the form available over the

counter is useful for protection of bones, but 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.

--

ne Holden, MS, RD < fivestar@... >

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