Caffeic acid phenethyl ester against cadmium induced toxicity mediated by CircRNA modulates autophagy in HepG2 cells

Abstract

Cadmium pollution and poisoning are serious environmental and pharmacological concerns, and effective drugs can alleviate or offset cadmium-induced toxicity are badly needed. In this study, Caffeic acid phenethyl ester (CAPE), a major active component of propolis, showed protective effect against CdCl₂-induced toxicology by suppressing autophagy in HepG2 cells. CircRNAs are increasingly perceived as vital regulators in the process of autophagy. However, it remain unclear whether circRNAs are involved in CAPE's protection against CdCl₂-induced autophagy. Under this context, the roles of CircRNA (hsa_circ_0040768) in CAPE's protection against CdCl₂-induced damage were investigated by PCR and Western blot. Results showed that CAPE significantly (P < 0.05) increased cell viability via inhibiting CdCl₂-induced autophagy, and this process was regulated by hsa_circ_0040768/MAP1LC3B axis. Overexpressing hsa_circ_0040768 led to reduced cell viability and increased autophagy in CAPE-treated HepG2 cells exposed to CdCl₂. In contrast, silencing hsa_circ_0040768 showed similar protective effect to CAPE. These results show for the first time the involvement of the hsa_circ_0040768/MAP1LC3B axis in the CAPE's protection against CdCl₂-induced autophagy, and provide novel insights into the pathogenesis and potential prevention/treatment of cadmium-associated diseases.

Keywords: Autophagy; Cadmium; Caffeic acid phenethyl Ester; Hsa_circ_0040768; MAP1LC3B.