Anti-cancer effects of bioactive compounds from rose hip fruit in human breast cancer cell lines

Rose hips have long been used in human diets as a food ingredient and supplement. Their multiple medical properties, which have been attributed to their abundant carotenoid composition, have attracted widespread scientific attention. This thesis examined the carotenoid composition in rose hips from five rose species. The anti-cancer effect of different carotenoid fractions from rose hips was investigated in human breast cancer cell lines, using the natural variation in carotenoid content in hips from different rose species. Based on the results obtained, representative single carotenoids were selected for further investigation. A rapid, effective method was developed using a HPLC-DAD-APCI+-MS system for carotenoid identification and quantification in rose hips. Twenty-one carotenoids, including 11 xanthophylls and 10 carotenes, were detected in saponified extract and 23 carotenoid esters in unsaponified extract from hips of the five rose species. Three fractions were subsequently isolated from total carotenoid extract of rose hips and their anti-proliferative activities were investigated in human breast cancer cell lines. Xanthophyll ester fraction was proved more potent than lycopene isomer or an undefined carotene fraction. Rosa multiflora Thunb. hips were the most effective, giving low IC50 values in MTT assay, and a unique xanthophyll ester pattern was found in this species. When xanthophyll ester was combined with triterpenes in MTT assay, synergistic effects were found in the MCF-7 cancer cell line. A significant synergistic effect was also found on combining a 10 µM concentration of rose hip triterpene fraction with 50 µM ascorbate, which resulted in strong inhibition in cell proliferation in MCF-7 cell line, while normal-like cells MCF-10A were relatively undamaged. Xanthophyll esters were verified to be more effective than free xanthophylls in MTT assay comparing lutein and zeaxanthin with their esters. The xanthophyll ester fraction from R. multiflora and individual xanthophyll esters were found to decrease cancer stem cell sub-populations and inhibit cell migration. Xanthophyll esters were suggested to affect breast cancer cells by a mechanism involving the NF-κB pathway. Overall, these results support the beneficial health effects of rose hips and reveal potential to involve xanthophyll esters in future breast cancer therapy