Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against several human
cancer cell lines. In the present study, we investigated further possible mechanisms by which
dideoxypetrosynol A exerts its anti-proliferative action in cultured human
leukemia U937 cells. Exposure of U937 cells to
dideoxypetrosynol A resulted in growth inhibition and induction of apoptosis as measured by hemocytometer counts, fluorescent microscopy,
agarose gel electrophoresis and flow cytometry analysis. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression and activation of
caspase-3 and
caspase-9.
Dideoxypetrosynol A decreased the levels of
cyclooxygenase (COX)-2
mRNA and
protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in
prostaglandin E2 (
PGE2) synthesis. Furthermore,
dideoxypetrosynol A treatment markedly inhibited the activity of
telomerase, and the expression of human
telomerase reverse transcriptase (hTERT), a main determinant of the
telomerase enzymatic activity, was progressively down-regulated by
dideoxypetrosynol A treatment in a dose-dependent fashion. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-
cancer activity of
dideoxypetrosynol A.