Dibenzoylmethane, hydroxydibenzoylmethane and hydroxymethyldibenzoylmethane inhibit phorbol-12-myristate 13-acetate-induced breast carcinoma cell invasion

Dibenzoylmethane (DB), a minor constituent of the root extract of licorice, belongs to the flavonoid family. Hydroxydibenzoylmethane (HDB) and hydroxymethyldibenzoylmethane (HMDB) have an identical structure to DB, but also possess a hydroxyl group and a hydroxyl and methyl group bonded to aromatic rings, respectively. They inhibit cellular proliferation and induce apoptosis in a variety of types of cancer cell, however, the antimetastatic effects of DB, HDB and HMDB on human breast carcinoma cells remain to be elucidated. The present study aimed to clarify the molecular mechanisms underlying the effects of DB and its analogues on phorbol-12-myristate 13-acetate (PMA)-induced MCF-7 cell metastasis. The results revealed that DB, HDB and HMDB inhibited cell migration and invasion. In addition, PMA-mediated MCF-7 cell invasion was inhibited by DB, HDB and HMDB by inhibiting the expression of matrix metalloproteinase (MMP)-9. Rottlerin, a protein kinase C (PKC)δ inhibitor and LY294002, a phosphatidylinositide 3-kinase (PI3K) inhibitor, reduced the PMA-mediated expression of MMP-9 and cell invasion. Furthermore, DB, HDB and HMDB prevented the activation of PKCδ and PI3K by inhibiting their phosphorylation. The present study was the first, to the best of our knowledge, to demonstrate the antimetastatic potential of DB, HDB and HDMB, which decreased cancer cell invasion through the PI3K/PKCδ-mediated MMP-9 pathway.