Anacardic Acid Ameliorates Anti-Inflammatory and Antioxidant Signaling Pathways in Human Hepatocellular Carcinoma HepG2 ARE Cells

Background

Anacardic Acid (AA) is derived from cashew kernel shells and cashew apples and recognized for its extensive pharmacological properties, which include significant antitumor activity. Previous studies have established the anticancer efficacy of AA across other malignancies; however, its specific function and the underlying mechanisms in hepatic cancer are still to be thoroughly investigated.

Materials and Methods

HepG2-ARE hepatocellular carcinoma cells were treated with different concentrations of AA and subjected to luciferase, MTS, glucose uptake, cell migration, Western blot and immunofluorescence assays to assess the effect of AA on NRF2 activation, cell viability, glucose uptake, cell migration and protein expression respectively.

Results

We found that AA significantly lowered the vitality of hepatic cancer cells and their ability to take up glucose. Furthermore, AA inhibited the migratory ability of cancer cells and activated the NRF2 signaling pathway, resulting in the upregulation of antioxidant enzymes, including SOD1, NQO1, and HO1. It also regulated the PI3K/AKT/mTOR and Wnt/β-catenin pathways essential to the growth and survival of cancer cells. AA reduced phosphorylated NF-κB and proinflammatory cytokines, attenuating NF-κB signaling in inflammation, and activated MAPK/JNK signaling by increasing phosphorylation of p38 and JNK. Immunofluorescence examination substantiated reduced phosphorylated NF-κB levels in AA-treated cells relative to untreated controls, corroborating its function in NF-κB pathway suppression.

Conclusion

These results indicate that AA has potential as a therapeutic agent by modulating multiple signaling pathways, which may result in potent anticancer effects against hepatic carcinoma. Nonetheless, additional in vivo investigations are required to confirm its effectiveness and clinical relevance.