Involvement of miRNAs in response to oxidative stress induced by the steroidal glycoalkaloid α-solanine in hepatocellular carcinoma cells.

Abstract

α-Solanine is a natural toxic glycoalkaloid produced in some species of the Solanaceae family with antiproliferative activity in various cancers. This study aimed to investigate the effect of α-solanine on the oxidative stress status in human hepatocellular carcinoma HepG2 cells and to evaluate its influence on microRNAs (miRNAs) associated with oxidative stress and NF-κB regulation. The prooxidant effect of α-solanine was tested by the decay rate of the fluorescent probe, β-phycoerythrin, and by measuring malondialdehyde, reduced Glutathione, catalase, and superoxide dismutase following treatment of HepG2 cells with low doses of α-solanine. Immunocytochemical techniques were used to detect mitochondrial membrane potential (ΔΨm) and NF-κB protein. The gene expression of NF-κB and miRNAs was evaluated by real-time PCR. α-Solanine is a prooxidant that causes a rapid decay in the fluorescence intensity of β-phycoerythrin. It induces oxidative stress-related alterations such as increased lipid peroxidation and reduced antioxidant markers. Oxidative stress induced by α-solanine was mediated by decreased ΔΨm, increased NF-κB expression, upregulation of miRNAs that control oxidative stress by regulating the NF-κB pathway, and downregulation of oncogenic miRNAs that inhibit the NF-κB pathway. α-Solanine-induced oxidative stress is mediated by alterations in the NF-κB pathway with a detected crosstalk between α-solanine treatment and the expression of oxidative stress-responsive miRNAs.