Honokiol inhibits the EGFR signaling pathway and downregulates STAT3 target genes in multidrug-sensitive and -resistant cells.

<p>KB-3-1 and KB-8-5 cells were treated with 5 µg/ml of honokiol for short time (0.5, 1, or 2 h) or long time (24, 48, or 72 h). Whole cell lysates were immunoblotted for the indicated proteins. The effect of honokiol at early time points: (<b>a</b>) phosphorylation of EGFR and STAT3; (<b>b</b>) Honokiol decreases phosphorylation of AKT and ERK. The effect of honokiol at late time points: (<b>c</b>) phosphorylation and expression of EGFR and STAT3; (<b>d</b>) phosphorylation and expression of AKT and ERK; (<b>e</b>) expression of survivin, Bcl-2, Mcl-1. (<b>f</b>) Honokiol inhibits the EGFR signaling pathway and downregulates STAT3 target genes in a dose-dependent manner. KB-3-1 and KB-8-5 cells were treated with 5, 10, 15 µg/ml of honokiol for 48 h. Whole cell lysates were immunoblotted for the indicated proteins. (<b>g</b>) Honokiol inhibits the EGFR-STAT3 pathway in KB-C1 and KB-V1 cells. KB-C1 and KB-V1 cells were treated with 5, 10, 15 µg/ml of honokiol for 48 h. All experiments were repeated at least three times, and representative data are presented.