Thymoquinone enhances the antioxidant and anticancer activity of Lebanese propolis

BACKGROUND: Reactive oxygen species (ROS) are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants. In recent years, the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer. Propolis, a resinous honeybee product, has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms. AIM: To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone (TQ) the main constituent of Nigella sativa essential oil. METHODS: Crude extracts of Lebanese propolis collected from two locations, Rashaya and Akkar-Danniyeh, were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu method. The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and to inhibit H(2)O(2)-induced oxidative hemolysis of human erythrocytes. The anticancer activity was evaluated by [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] MTT assay against HCT-116 human colorectal cancer cells and MDA-MB-231 human breast cancer cells. RESULTS: The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81 µg and 83.503 µg of gallic acid equivalent /mg of propolis, respectively. Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H(2)O(2)-induced hemolysis. They also dose-dependently decreased the viability of both cancer cell lines. The IC(50) value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3, 61.7, 40.44 µg/mL for breast cancer cells at 72 h and 33.3, 50.9, 33.5 µg/mL for colorectal cancer cells at the same time point, respectively. Importantly, the inhibitory effects of propolis on DPPH radicals and cancer cell viability were achieved at half its concentration when combined with TQ. CONCLUSION: Our results indicate that Lebanese propolis extract has antioxidant and anticancer potential and its combination with TQ could possibly prevent ROS- mediated diseases.