Catalase Induced by All-Trans Retinoic Acid Is Involved in Antiproliferation of 36B10 Cells

목 적: 레티노인산(All-trans retinoic acid, ATRA)은 뇌종양 세포의 증식을 억제한다. 최근 ATRA에 의한 카타라제의 유도가 보고된 바 있다. 이에 저자들은 ATRA의한 카타라제의 유도가 ATRA의 세포증식 억제 효과와 관련이 있는지 알아보고자 하였다. 대상 및 방법: 36B10세포를 0∼50μM ATRA로 24, 48시간 처리한 후 카타라제의 mRNA, 단백질 및 활성도를 측정하였다. 반응성산소종(reactive oxygen species, ROS)은 2',7'-dichlorofluorescin diacetate를 사용하여 측정하였고, 세포사는 clonogenic assay로 측정하였다. 결 과: 카타라제의 mRNA, 단백질 및 활성도는 ATRA의 농도 및 처리 시간에 따라 증가하였다. ATRA에 의해 증가한 카타라제의 활성도는 3-amino-1,2,4-triazole (ATZ)에 의해 감소하였다. ATRA에 의해 증가한 ROS는 ATZ에 의해 감소하였다. ATRA에 의해 감소한 세포 생존분획은 ATZ에 의해 부분적으로 증가하였다. 결 론: ATRA에 의해 유도된 카타라제는 ROS의 과생산과 관련 있으며 이는 36B10세포의 증식 억제를 가져온다.

Purpose: All-trans retinoic acid (ATRA) has antiproliferative effects against brain tumor cells. Recently, ATRA has been reported to induce catalase. We investigated whether catalase induction by ATRA is associated with its antiproliferative effects. Materials and Methods: 36B10 cells were exposed to 0∼50μM ATRA for 24 or 48 hours and mRNA, protein, and activity of catalase were measured. Reactive oxygen species (ROS) were measured using 2',7'-dichlorofluorescin diacetate. A clonogenic assay was used to confirm the cytotoxic effect. Results: The mRNA, protein, and activity of catalase were found to increase in a concentration- and incubationtime-dependent manner. The increase in catalase activity induced by ATRA was decreased by the addition of 3-amino-1,2,4-triazole (ATZ). ROS was also increased with ATRA and decreased by the addition of ATZ. The decrease in cell survival induced by ATRA was partly rescued by ATZ. Conclusion: Catalase induction by ATRA is involved in ROS overproduction and thus inhibits the proliferation of 36B10 cells.