Abstract
Cancer is one of the leading health problems worldwide with hepatic cancerbeing one of the most common cancers. To date, a number of anti-cancer agents have been employed for chemotherapeutic purposes one of which includes cyclophosphamide (CP). Because of the serious side effect of CP, this study aims to investigate the potential protective effect of coenzyme-10 (CoQ10) and piperine (PIP) against cytotoxicity induced by CP in HuH-7 cell line. Based on IC50, 10, 12, 10, and 12 µg/ml of CP, PIP, CoQ10, PIP + CoQ10 were selected for further investigations. MTT and NRU assays results showed the combinations of CP + PIP, CP + CoQ10, CP + PIP + CoQ10 demonstrated a potential cytotoxic effect on HuH-7 cells. Also, these drug combinations induced apoptosis and relative migration rate compared with CP as evaluated by TUNEL and wound healing assays respectively. Furthermore, mitochondrial membrane potential (MMP) indicated the three drug combinations improved the mitochondrial membrane permeability in HuH-7cells. Finally, upregulation of bcl-2, caspase-3 caspase-8, caspase-9 and p53 genes in HuH-7 cells were observed in the drug combination treatments compared to CP alone, confirming the positive effect of PIP and CoQ10 when combined with CP. In conclusion, current results showed that PIP and CoQ10 have anti-cancerous properties and may be a useful resource for effective remedies in the treatment of liver cancer.