Lower concentrations of curcumin inhibit Her2-Akt pathway components in human breast cancer cells, and other dietary botanicals potentiate this and lapatinib inhibition.

ABSTRACT

Her2-dependent breast cancer is treated with pharmacological drugs (eg, Herceptin, lapatinib) that target Her2 signaling. Curcumin has emerged as a potential co-treatment for this and other cancers, but prior studies have focused on non-attainable concentrations. Here we test the hypothesis that attainable in vivo levels of dietary curcumin can reduce Her2 signaling. Consistent with previous studies, higher dose curcumin (18 µmol/L) inhibits Her2-Akt pathway signaling (pHer2, total Her2 and pAkt levels) and cell growth using AU565 human breast cancer cells. We then examined lower, more physiologically relevant concentrations of curcumin, alone and in combination with other dietary botanicals (quercetin and OptiBerry fruit extract). At 4 µmol/L, curcumin reduced Her2 signaling, and even more when combined with quercetin or OptiBerry. At 1.5 µmol/L curcumin, pHer2 and Her2 (but not pAkt) were reduced, with all three pathway markers reduced more in the presence of quercetin. We also found that 1.5 µmol/L curcumin strongly potentiated lapatinib inhibition of Her2-Akt pathway signaling, and more so for pAkt, when combined with quercetin plus OptiBerry (CQO). Parallel analyses revealed cell growth inhibition at 18 and 4 µmol/L but not 1.5 µmol/L curcumin, and potentiation of 1.5 µmol/L curcumin growth arrest with other botanicals +/- lapatinib. These studies demonstrate that a physiological attainable level of curcumin (1.5 µmol/L) can reduce some components of the critical Her2-Akt pathway; that even more complete inhibition can be achieved by combination with other dietary botanicals; and that curcumin and other botanicals can potentiate the action of the Her2-cancer metastatic drug lapatinib, in turn suggesting the potential anti-cancer clinical use of these botanicals.