Pigments from Uroleucon nigrotuberculatum Induce Apoptosis in HL60 Human Leukemia Cells, Implicating Intracellular Oxidative Stress and Activation of Caspases

Abstract

Two pigmented compounds from Uroleucon nigrotuberculatum, rhododactynaphin-jc-1 (H427) and rhododactynaphin-jc-2 (H373), significantly diminished the cell viability of HL60 cells with IC₅₀ of 10 μM and 30 μM, respectively, in an 18 h-dye uptake assay. Both H427 and H373 augmented the levels of intracellular reactive oxygen species (ROS) and induced apoptosis as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis. ROS augmentation by both H427 and H373 was inhibited by N-acetylcysteine (NAC) and α-tocopherol. The apoptosis induced by H427 was inhibited efficiently with NAC and caspase-8 inhibitor but less efficiently with α-tocopherol and caspase-9 inhibitor. These findings suggested that these pigments have pro-apoptotic activities via oxidative stress.