Piceatannol에 의한 인체 혈구암세포의 증식 억제 및 telomerase 활성 저하

Abstract

이상의 연구 결과에 의하면 piceatannol의 처리에 의한 U937 세포의 증식억제는 세포주기 S기 arrest 및 apoptosis 유발과 뚜렷한 연관성이 있었다. 또한 piceatannol은 hTERT 및 TEP-1 유전자의 발현 저하와 연관된 telomerase 활성의 저하 효과도 나타내었으나, COXs의 발현 및 PGE2의 생성에는 큰 변화를 주지 못하였다. 따라서 본 연구의 결과는 암세포에서 높게 발현되는 telomerase 활성 조절제로서 piceatannol의 적용이 가능함을 보여주며, 이는 piceatannol의 항암작용을 이해하는데 매우 유용한 자료라 생각한다. Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the anti-cancer potency of piceatannol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail. In the present study, we investigated further possible mechanisms by which piceatannol exerts its anti-proliferative action in cultured human leukemia U937 cells. Exposure of U937 cells to piceatannol resulted in growth inhibition and induction of apoptosis as measured by MTT assay and flow cytometry analysis, which was associated with S phase arrest of the cell cycle. Piceatannol treatment markedly inhibited the activity of telomerase, and the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1), main determinants of the telomerase enzymatic activity, were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. However, the levels of cyclooxygenases (COXs) expression and prostaglandin E2 (PGE2) release were not changed in piceatannol-treated U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of piceatannol.