Antioxidant and apoptotic activities of sitagliptin against hepatocellular carcinoma: An in vitro study [version 1; peer review: 1 approved with reservations]

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 causes 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. After an incubation period for 48 hours, the supernatants were collected to quantify the level 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 significantly decreased 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. Conclusions: Sitagliptin showed apoptotic and antioxidant activity against HCC which may potentiate chemotherapeutic agents like cisplatin, in addition to reducing the oxidative stress against normal cells.