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

• Published in: Environmental toxicology 2022-02, Vol.37 (2), p.212-223
• Main Authors: Gouhar, Shaimaa A., Abo‐elfadl, Mahmoud T., Gamal‐Eldeen, Amira M., El‐Daly, Sherien M.
• Format: Article
• Language: English
• Subjects: Antioxidants; Apoptosis; Cancer; Carcinoma, Hepatocellular - genetics; Catalase; Cells; Crosstalk; Decay; Decay rate; Evaluation; Fluorescence; Fluorescent indicators; Gene expression; Glutathione; glycoalkaloid; Glycoalkaloids; Hep G2 Cells; Hepatocellular carcinoma; HepG2; Humans; Lipid peroxidation; Lipids; Liver cancer; Liver Neoplasms - genetics; Malondialdehyde; Membrane potential; MicroRNAs - genetics; miRNA; Mitochondria; Neoplasms; NF-kappa B - genetics; NF-kappa B - metabolism; NF‐κB; Nucleotide sequence; Oxidation; Oxidative Stress; PCR; Peroxidation; Solanine; Superoxide dismutase; α‐Solanine
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23390

Background α‐Solanine is a natural toxic glycoalkaloid produced in some species of the Solanaceae family with antiproliferative activity in various cancers. Objective 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. Methods 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. Results 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. Conclusion 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.