Antiinflammatory effects of cucurbitacins and sorafenib in Hepg2 cells by modulating the IκB/NF-κB/COX-2 pathway through Akt signaling.

Aim: Cucurbitacins possess antitumor, antiproliferative, and antiinflammatory properties. This study aims to examine the antiinflammatory effects of CuD, CuI, and CuE on NF-κB, iNOS, COX-2, and Akt and compare their cytotoxic and antiinflammatory effects on HepG2 cells with sorafenib, the primary chemotherapeutic agent used in HCC treatment. Methods: Cytotoxic effects of cucurbitacins and sorafenib on HepG2 cells were evaluated using MTT and LDH assays, along with Annexin V, MMP, and comet assays. Levels of proteins related to the Akt/NF-κB pathway and COX-2, iNOS, and NO were also measured. Results: Our study showed that CuD, CuI, CuE, and sorafenib have antiproliferative and cytotoxic effects on HepG2 cells. Cucurbitacins induced apoptosis at lower concentrations than sorafenib and, like sorafenib, reduced p-Akt, p-IκBα protein levels, and nuclear translocation of NF-κB in a dose-dependent manner. Moreover, all compounds significantly decreased COX-2, iNOS, and NO levels, especially at 5 μM concentration. Conclusion: These results indicate that cucurbitacins exert antiinflammatory effects on HepG2 cells by modulating the PI3K/Akt/NFκB signaling pathway, thereby reducing COX-2, iNOS, and NO levels. These effects are similar to those of sorafenib.