Double whammy of vitamin D and anti-inflammatory zaps prostate cancer cells

June 03, 2017

If their 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 includes ibuprofen, indomethacin and naproxen, as well as other so-called COX-2 inhibitors linked to increased risk for cardiovascular disease, including Vioxx and Celebrex.

David Feldman, M.D., professor of Medicine in the Division of Endocrinology, Gerontology and Metabolism at the Stanford University School of Medicine, says as NSAIDs have their own risks, care must taken even with lower doses and it would still be necessary to watch patients very closely if it is intended to keep them on these drugs for extended periods of time.

He says they are aiming to find doses that are less toxic and far more tolerable for the patient.

In the body prostaglandins are responsible for activating the inflammatory response that results in pain and fever, and 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 by first limiting the expression of a key enzyme needed to synthesize prostaglandins into COX-2, and secondly, by increasing the expression of an enzyme that rapidly disassembles active prostaglandin molecules, thus promoting the breakdown of the hormone.

The scientists also discovered that calcitriol inhibited the production of two cell receptors used by prostaglandins to regulate gene expression and control tumor proliferation.

Even though the scientists were able to show that activated vitamin D, calcitriol, worked by itself to limit prostate cancer growth, they saw it was equally effective in much smaller doses when used in combination with NSAIDs.

Furthermore, the calcitriol dramatically reduced the amount of NSAIDs necessary to curb prostate cancer cell growth.

This discovery is particularly important now, in view 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, before Feldman and his colleagues can advocate the treatment for patients, they need to verify that vitamin D and NSAIDs work in synergy not just in these cell lines, and also work in the same manner, in humans.

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.

The study is published in the journal Cancer Research.