Anti oxidant and apoptotic activities of sitagliptin v1

Abstract Background: Hepatocellular carcinoma (HCC) is the most common and aggressivetype of liver cancer. Most chemotherapeutic medications nowadays implyoxidative stress leading to toxicity, which raises the necessity to find agentswith better safety profiles against normal cells in addition to theiranticancer activity. Sitagliptin has been shown to possess antioxidant as wellas apoptotic properties by the specific suppression of dipeptidyl-peptidase 4,a glycoprotein produced in many tissues that have been thought to promote tumorigenesisand metastasis. Methods: Five groups of cell-lines wereincluded: Control (untreated HepG2 cells); cisplatin treatment HepG2 cells;sitagliptin treated HepG2 cells; combination of different concentrations ofcisplatin plus sitagliptin (250 μg/ml) treated HepG2 cells, and finally, combinationof different concentrations of sitagliptin plus cisplatin (25 μg/ml) treatedHepG2 cells. Then after incubation period for 48 hours, the supernatants werecollected to assess malondialdehyde (MDA) and B-celllymphoma-2 (BCL-2) by ELISA assay kits. Data were finally gathered and analyzed statistically. Results: Our findings indicated thatsitagliptin decreased significantly the oxidative stress, particularly at highconcentrations, through decreasing the MDA level. In addition, sitagliptinexhibited significant apoptotic activity against HepG2 cells through decreasingBCL-2 level. In combination with cisplatin, sitagliptin significantlypotentiated the apoptotic effect and reduced the oxidative stress parameters. Conclusion: Sitagliptin showedapoptotic and antioxidant activity against HCC which may potentiatechemotherapeutic agents like cisplatin, in addition to, reduce the oxidativestress against normal cells.