Apigenin, a Partial Antagonist of the Estrogen Receptor (ER), Inhibits ER-Positive Breast Cancer Cell Proliferation through Akt/FOXM1 Signaling

International Journal of Molecular Sciences

Frédéric Percevault¹  YannLe Page¹  Gilles Flouriot¹  Farzad Pakdel¹  François Ferrière¹  ThuHa Pham¹ 

[1]Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, Rennes University, F-35000 Rennes, France

关键词: breast cancer;    endocrine resistance;    ER;    Akt;    FOXM1;    phytochemicals;   

DOI  :  10.3390/ijms22010470

来源: DOAJ

【 摘 要 】

Approximately 80% of breast cancer (BC) cases express the estrogen receptor (ER), and 30–40% of these cases acquire resistance to endocrine therapies over time. Hyperactivation of Akt is one of the mechanisms by which endocrine resistance is acquired. Apigenin (Api), a flavone found in several plant foods, has shown beneficial effects in cancer and chronic diseases. Here, we studied the therapeutic potential of Api in the treatment of ER-positive, endocrine therapy-resistant BC. To achieve this objective, we stably overexpressed the constitutively active form of the Akt protein in MCF-7 cells (named the MCF-7/Akt clone). The proliferation of MCF-7/Akt cells is partially independent of estradiol (E2) and exhibits an incomplete response to the anti-estrogen agent 4-hydroxytamoxifen, demonstrating the resistance of these cells to hormone therapy. Api exerts an antiproliferative effect on the MCF-7/Akt clone. Api inhibits the proliferative effect of E2 by inducing G2/M phase cell cycle arrest and apoptosis. Importantly, Api inhibits the Akt/FOXM1 signaling pathway by decreasing the expression of FOXM1, a key transcription factor involved in the cell cycle. Api also alters the expression of genes regulated by FOXM1, including cell cycle-related genes, particularly in the MCF-7/Akt clone. Together, our results strengthen the therapeutic potential of Api for the treatment of endocrine-resistant BC.

【 授权许可】

Unknown