In-vitro apoptotic and metastatic effect of ibuprofen on hepatocellular carcinoma cells

Abstract

Ibuprofen (2RS)­1 [4­(2­methylpropyl)phenyl] propionic acid is the first derivative of propionic acid developed in 1969 as an alternative to aspirin. In the literature, it has been determined that ibuprofen has a favorable effect on long­term use of small doses of neuro­degenerative diseases such as Alzheimer's and Parkinson's disease, and at the same time, daily intake of ibuprofen produces risk reductions for colon, breast, lung, and prostate cancer. However, the metastatic and apoptotic effects of ibuprofen on human Hapatocellular Carcinoma Cells (Hep3B) have not been studied yet. Therefore, in this study, we aimed to investigate the metastatic and apoptotic properties of ibuprofen in Hep3B cells. For this purpose, ibuprofen was exposed to Hep3B cells with different doses (150 µg/mL, 75 µg/mL, 39 µg/mL, 18 µg/mL, and 9 µg/mL) at different time points (24 h and 48 h). Cell proliferation was determined with the MTT assay. Apoptotic effect of ibuprofen was analyzed with the real­time PCR method at the mRNA level of Bcl­2, Bcl­XL and Bax expressions. A scratch assay was performed to investigate the metastatic effect of ibuprofen (150 µg/mL and 9 µg/mL) on Hep3B cells. As a result, ibuprofen inhibited cell proliferation in a dose­ and time­dependent manner. The IC50 values were 75 µg/mL for 24 h and 32.5 µg/mL for 48 h. In addition, Bax expression was upregulated as a result of the administration of a high dose of ibuprofen and a decreased level of Bcl­2 and Bcl­XL mRNA expression. Consistent with these results, the cell migration capability of Hep3B cells was inhibited at 150 µg/mL of ibuprofen doses. These findings suggest that ibuprofen has an anti­cancer effect on Hep3B cells at the highest doses.