RAc, TRAIL lead to adenoma cell death and fewer polyps in mice, cell death in human polyps-- Eric Metcalf
Tuesday, March 30, 2010 (Last Updated: 03/31/2010)
TUESDAY, March 30 (HealthDay News) -- A combination of two drugs trigger cell death in human colon polyps, suggesting an approach for the chemoprevention of colorectal cancer, according to research published online March 28 in Nature.
Ling Zhang, Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues write that all-trans-retinyl acetate (RAc) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) kills precancerous polyps and inhibits tumor growth in ApcMin mice. The researchers investigated a short-term approach, finding that after two cycles of the combination in one week, ApcMin mice had a 69 percent reduction in the number of polyps two weeks later, and, when ten-fold higher doses were used, tumor numbers were reduced to 10 percent of the number in controls.
The researchers also treated biopsy samples from normal and tumor regions from patients with familial adenomatous polyposis, and found that treating normal slices with TRAIL and RAc didn't lead to significant cell death, but treating polyp samples did induce cell death. TRAIL and RAc killed 57 percent of the cells in the human colon polyps, on average.
"Induction of apoptosis represents a most potent cellular mechanism against cancer, and selectively eliminating premalignant tumor cells by TRAIL and RAc is an effective method of chemoprevention. More notably, we demonstrate that the chemopreventive effect of TRAIL and RAc can be achieved by short-term intermittent and non-continuous treatment cycles," the authors conclude.
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