Differential H2O2 Susceptibility and AQP9 Induction in HL-60 and Ku812F Cell Lines Exposed to Hemp and Cranberry Extracts

Abstract

Acute myeloid leukemia (AML) is an aggressive hematological malignancy requiring novel treatments. Elevated baseline reactive oxygen species (ROS) and altered antioxidant defenses may render leukemic cells selectively vulnerable to pro-oxidant stress, potentially influenced by hydrogen peroxide (H2O2) transport through aquaporin 9 (AQP9). Plant polyphenols may further modulate oxidative stress. This study investigated the effects of H2O2 on cell survival, metabolic activity, and ROS levels in HL-60 and Ku812F cells in the presence of hemp (Cannabis sativa) and cranberry (Vaccinium macrocarpon) extracts obtained by cold maceration, ultrasound-assisted extraction, and supercritical fluid extraction. H2O2 reduced HL-60 metabolic activity to approximately 6% of untreated controls, increased ROS levels, and elevated AQP9 transcript levels 37.6-fold relative to DMSO-treated cells. These effects were absent from Ku812F cells. In H2O2-treated HL-60 cells, hemp and cranberry extracts further increased ROS without additional reductions in metabolic activity or survival. These findings associate H2O2-induced oxidative vulnerability with elevated ROS and AQP9 transcript levels in HL-60 cells, while extract-induced ROS increases were independent of the direction of AQP9 expression changes. Further assessment of baseline AQP9 levels, protein expression, and functional inhibition or knockdown is needed to establish its potential contribution to oxidative vulnerability.