Abstract
The low price and high contents of bioactive compounds in citrus peel increase interest in using it in various applications. Mandarin (Citrus reticluata) peel belongs to Rutaceae family and is rich with antioxidants. However, limited studies are available on toxicity of Mandarin peel oil (MPO) on human Prostate Cancer (PC3) cells. Therefore, the present study was conducted to study the cytotoxicity and genotoxicity of MPO on Human normal Fibroblast (HFB4) and PC3 cell lines. The half maximal inhibitory (IC50) and safe concentration of MPO was detected using MTT assay. Comet and DNA fragmentation assays were performed to assess apoptotic DNA damage. Also, the ROS level was evaluated and the mRNA expression level of apoptotic and antiapoptotic genes were measured using RT-PCR. Results of the cytotoxic test showed that MPO induced preferential inhibition of PC3 cells proliferation in a concentration-dependent manner with IC50 10.97 mu g/ml. The time-dependent induction of DNA breaks demonstrated in PC3 cells treated with MPO safe concentration-stimulated ROS generation and apoptotic DNA damage through increased expression of tumor suppressor p53 and Bax genes and decreased expression of Bcl2 and MDM2 genes. In contrast, non-significant changes were observed in the DNA integrity, ROS levels and expressions of the tested genes in the normal HFB4 cells treated with MPO. Thus, we concluded that MPO induced preferential cytotoxic and genotoxic effects toward cancerous PC3 with no noticeable toxic effects in normal HFB4 cells and therefore further in vivo studies are recommended to test its possible use as anticancer drugs.