Adding CYP24A1 inhibitors may improve antitumor activity of vitamin D

Apr 20 2016

Roswell Park Cancer Institute (RPCI) research on the most potent form of vitamin D, commonly called calcitriol, offers new insights into approaches that may enhance the antitumor activity of this much-studied human hormone. The researchers will share their findings in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2016, to be held April 16-20 in New Orleans.

Wei Luo, MD, PhD, a translational research scientist in the Department of Pharmacology and Therapeutics at Roswell Park, is the first author and Candace Johnson, PhD, President and CEO of the Institute, is the senior author of "Delineation of novel CYP24A1 transcriptional regulators" (abstract 866), which will be presented during a minisymposium on Sunday, April 17, at 4:15 p.m. CDT.

Calcitriol, an active vitamin D metabolite also known as 1,25-dihydroxyvitamin Dɜ (1,25Dɜ), has been shown to have limited antitumor impact in clinical trials. Looking to help explain the processes that may restrict the vitamin's anticancer efficacy, Dr. Luo and colleagues examined the impact of the overexpression of the enzyme CYP24A1. The researchers report that adding inhibitors of CYP24A1 may improve the antitumor activity of calcitriol.

After screening more than 55,000 compounds from a small-molecule library, the scientists identified four compounds shown to inhibit calcitriol. They then further examined the four compounds in prostate, bladder and kidney cancer cell lines. They found that the compounds CPI8 and CPI17 inhibited CYP24A1 at the transcription level and that CPI8 also increased the expression of a key protein that helps to inhibit cancer growth. The research team believes that inhibiting CYP24A1 expression may be a useful approach for enhancing the antitumor activity of vitamin D.

"We've known for years that vitamin D has the potential to help counteract and control cancer and sometimes has been shown to do so in the lab, but no one has been able to replicate those results in large clinical studies," says Dr. Luo. "So it's exciting to be able to isolate some of the dynamics that might be helping tumors to evade the anticancer benefits of vitamin D toward the goal of exploiting those processes and maybe learning how to overcome them."

Source: Roswell Park Cancer Institute