The active metabolite of vitamin D, calcitriol, and two other vitamin D analogs (QW-1624-F2-2 and paricalcitol) are promising chemopreventive agents, according to researchers from Roswell Park Cancer Institute.

They conducted both in vitro (outside the body) and in vivo (inside the body) studies to determine the effects of calcitriol and the analogs on the prevention of prostate cancer.

Inhibited Cell Growth

Calcitriol has been used clinically to treat a variety of disorders, including in recent clinical trials for established cancer.

However, a major obstacle to its clinical use is dose-limiting hypercalcemia -- an abnormally high concentration of calcium in the blood. The Vitamin D analogs -- QW, developed at John’s Hopkins University, and paricalcitol -- are less calcemic.

QW and paricalcitol have been shown to reduce the level of parathyroid hormones, which regulate the metabolism of calcium and phosphorus in the body.

In their in vitro studies, the researchers demonstrated that the three drugs inhibit cell growth, inhibit DNA synthesis, and promote cell cycle arrest.

Additionally, the vitamin D compounds regulated several proteins that affect tumor growth.

Slowed Progression

The researchers then studied the effects of calcitriol and QW on preventing androgen-dependent prostate cancer in mice that were programmed using the TRAMP (transgenic adenocarcinoma of mouse prostate) model to develop the disease as they aged.

Both calcitriol and QW slowed the progression of prostate cancer in intact TRAMP mice after 14 weeks of treatment as indicated by decreased reproductive tract and prostate weight.

In addition, chronic treatment of mice with calcitriol markedly reduced tumor burden, but siide effects were seen in some mice.

The effect of calcitriol and QW on hormone refractory prostate cancer also was investigated using castrated TRAMP mice. Results showed that vitamin D had no effect on disease progression in castrated mice as measured by reproductive tract and prostate weight.

Promising for Prevention

"Our pre-clinical data using the TRAMP mouse model, which mimics human prostate cancer, suggests that calcitriol and QW-1624-F2-2 are promising for prevention of androgen-dependent prostate cancer progression," says Adebusola Alagbala of Roswell Park Cancer Institute and lead author of the study.

"Further studies are under way in our laboratory to better understand how these agents prevent prostate cancer," Alagbala notes.

The studies, funded by the National Institutes of Health, were conducted in the laboratory of Dr. Barbara A. Foster at Roswell Park Cancer Institute.