Ebracteolatain A Exerts Anti-Proliferation of Breast Cancer by Inhibiting Protein Kinase D 1 in MEK/ERK and PI3K/AKT Signaling Pathways

BACKGROUND:Ebracteolatain A (EA) is an acetyl-phloroglucinol compound extracted from Euphorbiae Ebracteolatae Radix, which has been shown to have antitumor activity.PURPOSE:Current research addressed the antitumor activity of EA in breast cancer and further clarified its mechanism.STUDY DESIGN:Based on the pharmacodynamic evaluation in breast cancer cells and animal models, the antitumor effects of EA will be validated in vitro and in vivo.METHODS:Breast cancer cells were processed with increasing concentrations of EA. CCK-8 and colony formation assays were employed to examine the effects of EA on proliferation and survival. Flow cytometry detected the blocking function of EA on the cell cycle. The specific mechanism of EA in breast cancer was studied by transfection experiments and Western Blot analysis. Finally, a nude mice xenograft tumor model was constructed to assess the therapeutic and potential mechanism of EA.RESULTS:We proved that EA caused a dose-dependent inhibition on MCF-7 and MDA-MB-415 cells with IC50 of 6.164 and 6.623 μmol/l, respectively. While EA reduced cell proliferation and clone formation, and markedly arrested cells in the G0/G1 phase. In vivo, EA remarkably suppressed the tumor weight and volume in xenograft nude mice. Besides, PKD1 reversed the inhibition of EA on breast cancer cell proliferation, clone formation, and cycle arrest, and restored tumor growth in xenograft nude mice. Western Blot confirmed that EA regulates breast cancer by suppressing PKD1 in MEK/ERK and PI3K/AKT signaling pathways.CONCLUSION:Herein, we first confirmed EA exerts anti-proliferation by inhibiting PKD1 in MEK/ERK and PI3K/AKT signaling pathways, indicating that EA is a prodigious breast cancer drug candidate.