Caffeic acid phenethyl ester mitigates cadmium‐induced damage via the Hsa_circ_0010039/miR‐661/Caspase9 axis–mediated apoptosis

Abstract Caffeic acid phenethyl ester (CAPE) is a bioactive component of honeybee propolis, which has protective effect against heavy metal induced toxicology. Cadmium is a kind of heavy metal pollutant that is hazardous to human health especially liver, and apoptosis is an important mechanism related to cadmium injury. Circular RNAs (CircRNAs) are involved in the regulation of apoptosis. However, the protective effects of CAPE on cadmium‐induced cell apoptosis through CircRNA related mechanisms remains unclear at the current stage. In the present research, cell‐based studies revealed that treating HepG2 cells with CdCl2 (0–30 μM; 24 h) caused a dose‐dependent decrease in cell viability, and CAPE at 10 μM could reverse such a decrease. The circular RNA hsa‐circ‐0010039 may function as a ceRNA for the microRNA miR‐661 to enhance caspase 9 expression and regulate apoptosis. The anti‐apoptotic effects of CAPE against CdCl2‐induced injury may be achieved through inhibiting the expression of hsa‐circ‐0010039 and caspase 9 while up‐regulating miR‐661 expression. This is the first report on the involvement of circRNA in CAPE's alleviating effect on CdCl2‐induced injury and apoptosis. The hsa_circ_0010039/miR‐661/caspase9 axis deserves further research efforts especially in search of dietary interventions for cadmium injury.