Background: Hepatocellular carcinoma (HCC) is the most common and aggressive
type of liver cancer. Most chemotherapeutic medications nowadays imply
oxidative stress leading to toxicity, which raises the necessity to find agents
with better safety profiles against normal cells in addition to their
anticancer activity. Sitagliptin has been shown to possess antioxidant as well
as apoptotic properties by the specific suppression of dipeptidyl-peptidase 4,
a glycoprotein produced in many tissues that have been thought to promote tumorigenesis
and metastasis.
Methods: Five groups of cell-lines were
included: Control (untreated HepG2 cells); cisplatin treatment HepG2 cells;
sitagliptin treated HepG2 cells; combination of different concentrations of
cisplatin plus sitagliptin (250 μg/ml) treated HepG2 cells, and finally, combination
of different concentrations of sitagliptin plus cisplatin (25 μg/ml) treated
HepG2 cells. Then after incubation period for 48 hours, the supernatants were
collected to assess malondialdehyde (MDA) and B-cell
lymphoma-2 (BCL-2) by ELISA assay kits. Data were finally gathered and analyzed statistically.
Results: Our findings indicated that
sitagliptin decreased significantly the oxidative stress, particularly at high
concentrations, through decreasing the MDA level. In addition, sitagliptin
exhibited significant apoptotic activity against HepG2 cells through decreasing
BCL-2 level. In combination with cisplatin, sitagliptin significantly
potentiated the apoptotic effect and reduced the oxidative stress parameters.
Conclusion: Sitagliptin showed
apoptotic and antioxidant activity against HCC which may potentiate
chemotherapeutic agents like cisplatin, in addition to, reduce the oxidative
stress against normal cells.