Abstract:
: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.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Park C,Jung JH,Kim ND,Choi YHsubject
Has Abstractpub_date
2007-01-01 00:00:00pages
291-8issue
1eissn
1019-6439issn
1791-2423journal_volume
30pub_type
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