Inhibition of cyclooxygenase-2 and telomerase activities in human leukemia cells by dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp.
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.
Park
Cheol
C
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Korea.
Jung
Jee H
JH
Kim
Nam Deuk
ND
Choi
Yung Hyun
YH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007938:Leukemia; D047130:Petrosia; D053279:Polyynes / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014020:Tissue Extracts / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D005233:Fatty Alcohols; D014020:Tissue Extracts; D051028:bcl-2-Associated X Protein; C499970:dideoxypetrosynol A; D053279:Polyynes; D051546:Cyclooxygenase 2; D019098:Telomerase