SAN FRANCISCO—When combined with TRAIL (TNF-related apoptosis-inducing ligand), resveratrol—an antioxidant and anti-inflammatory flavinoid found in red wine—promotes apoptosis in a variety of cancers, including difficult-to-treat brain cancers, according to a study presented at the 93rd Annual Meeting of the American Association for Cancer Research (abstract 4238).
"Treatment with either compound alone induced only minimal apoptosis, but in combination, the two substances exerted a stronger response, triggering apoptosis and inhibiting cell growth even in TRAIL-resistant cells in a range of human brain tumors implanted in mice," said Klaus Michael Debatin, MD, PhD, chair, Department of Pediatrics, University of Ulm.
Pretreatment with p21 antisense oligonucleotides eliminated the synergistic effect of TRAIL and resveratrol in the brain tumors, whereas ectopic expression of p21 or pretreatment with the G1 cell cycle inhibitor mimosine strongly enhanced TRAIL-induced apoptosis.
This led the scientists to conclude that the combined treatment worked because of rapid induction of p21, causing G1 cell cycle arrest, said co-researcher Simone Fulda, MD, of University Children’s Hospital, Ulm.
"Apparently apoptosis can be accelerated if cells are kept in certain stages of the cell cycle," Dr. Debatin said. "And if you put on some brakes, you can suddenly induce sensitivity for cell apoptosis in response to TRAIL, even in cells that have not been very sensitive."
The study proved, for the first time, that apoptosis sensitivity and cell cycle regulation are somehow linked, the scientists said. "Studies of these areas may provide insight into the defects present in tumor cells and how to interefere with tumor cell growth," Dr. Debatin said.
