The Evaluation of Safety Property and Apoptotic Efficacy of alpha-L-Guluronic Acid (G2013), as a Novel NSAID, Under In Vitro Examination on L929 and Hepatocellular Carcinoma Cell Lines

Background: Many investigations have expanded this concept that liver chronic inflammation has an essential role in persistent cell damages along with altering the liver microenvironment leading to fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). To reduce inflammation and relieve symptoms, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used; however, their long-term usage can lead to severe adverse events on vital organs like the liver. Interestingly, the alpha-L-Guluronic Acid (G2013), as a novel NSAID with immunomodulatory properties, has shown the inhibitory effects on inflammation and metastasis in experimental models. Objective: This study was conducted to determine the effects of G2013 on cytotoxicity and induction of apoptosis, as a new therapeutic target for cancer therapy, in the HepG2 cell line and the mouse fibroblast cell line L929, as a control. Methods: MTT assay and flow cytometry method were carried out using the different concentrations of G2013 (5, 15, 25, 50, 100, 200 and 400 mu g/ml) in 3 distinct incubation times. Results: Our data showed that treatment of HepG2 cells with high concentration (400 mu g/mL) of G2013 could effectively cause a decrease in cell viability, so that they were statistically different after 72 hours compared to other concentrations (5 to 200 mu g/ml) (p<0.05 andp<0.01, respectively). Moreover, the proportion of apoptosis of HepG2 cells at the dose of 200 mu g/mL considerably increased, suggesting that the induction of apoptosis by G2013 in HepG2 cells is dose-and time -dependent, which could promote its anticancer properties. Conclusion: The present study revealed that G2013 could induce apoptosis in the liver cancer model. Therefore, based on these findings, G2013 might be considered as a therapeutic option in cancer therapy.