Chemopreventive effect of flavonoids from Ougan (Citrus reticulata cv. Suavissima) fruit against cancer cell proliferation and migration

Citrus reticulata cv. Suavissima (Ougan) is a rich source of flavonoids, and its peel has been employed as a traditional Chinese medicine for a long time. Among the different fruit parts, namely flavedo, albedo, segment membrane and juice sacs, flavedo showed significant inhibitory effect on three cancer cell lines (HepG2, HL-60 and MDA-MB-231). Three flavanone glycosides, naringin, hesperidin, neohesperidin as well as four polymethoxylated flavones (PMFs), sinensetin, nobiletin, tangeretin and 5-demethylnobiletin were separated and purified from Ougan flavedo and identified by HPLC-DAD and LC-MS. Cytotoxicity assay showed that two flavanone aglycones and four PMFs exhibited significant antiproliferative activity on the three cancer cells. Structure-activity relationship was observed for the Ougan flavonoid-mediated antiproliferative activity. Wound healing assay showed that nobiletin and tangeretin exerted inhibitory effects on SKOV3 cell migration as well. These results indicate that Ougan flavonoids may have preventive or therapeutic potential for inhibiting cancer cell proliferation and migration.