All-trans retinoic acid (ATRA) is a derivative of vitamin A and exhibits anticancer activity against acute promyelocytic leukemia. Fenbendazole (FBZ) is a benzimidazole anthelmintic that has wide safety margin and low toxicity. Recently, FBZ has been found to have anticancer activity by destabilizing microtubules. In this study, we treat ATRA and FBZ on HL-60 cells, a human leukemia cell line, to investigate the synergistic effects of two drugs, and the potential anticancer mechanism. ATRA and FBZ significantly decreased the metabolic activity of HL-60 cells at 0.04 μM ATRA. Cell viability of ATRA-treated HL-60 cells decreased in a concentration-dependent manner and more decreased by FBZ. N-acetyl cysteine, an inhibitor of reactive oxygen species production, significantly increased the metabolic activity of the cells treated with ATRA and FBZ. Hoechst 33342 and propidium iodide staining showed the presence of broken nuclei in the HL-60 cells treated with ATRA and FBZ. And also, an apoptosis analysis demonstrated that 0.2 μM FBZ increased the percentages of cells in apoptosis and necrosis. In contrast, 0.04 μM ATRA showed no significant difference. Based on multiple assays, ATRA and FBZ showed not synergistic, but additive effect on HL-60 cells. This study may provide researchers and clinicians in cancer-related fields with some valuable information regarding the application of ATRA and FBZ.

서 론
재료 및 방법
세포와 물질 처리
세포의 대사 활성도 및 생존율 측정
유세포 분석
Hoechst 33342와 PI용액을 이용한 세포의 핵 염색
통계처리
결 과
ATRA와 FBZ을 처리한 HL-60 세포에서 ROS의 효과분석
Hoechst 33342과 PI 염색을 통한 세포핵 분석
ATRA와 FBZ 처리에 따른 세포사 분석
고 찰

• Chan-Hee Lee(Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Jeju National University, Jeju-si, Jeju 63243, Republic of Korea)
• Hong-Gu Joo(Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Jeju National University, Jeju-si, Jeju 63243, Republic of Korea, Veterinary Medical Research Institute, Jeju National University, Jeju-si, Jeju 63243, Republic of Korea) Corresponding author