Several naturally occurring or synthesized forms of chalcone have been shown to possess multiple biological properties, including antitumor activities. A novel synthetic flavonoid, the benzochalcone derivative DK-78, was administered with the anticancer drug doxorubicin to two breast cancer cell lines (MCF7-VN and MDA-MB-231), and was evaluated for a synergistic cytotoxic effect. DK-78 reduced the expression of mesenchymal marker proteins and reduced cell migration and attachment. Sequential treatment with DK-78 and doxorubicin showed synergistic effects.