SAN FRANCISCOWhen combined with TRAIL (TNF-related apoptosis-inducing
ligand), resveratrolan antioxidant and anti-inflammatory flavinoid found in
red winepromotes 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.