Background: Phytoestrogens have been proposed as replaceable medicines for climacteric
hormone replacement therapy, on the basis of EP3138562 and US5516528. However, recent studies
demonstrated that phytoestrogens might promote the proliferation of breast cancer cells, which is
rooted in their estrogenic activity. Acacetin, as one phytoestrogen, has been reported to exhibit estrogenic
activity. But the effect of acacetin on breast cancer cells proliferation and its mechanism has not
Objective: This study aims to evaluate the effects of acacetin on breast cancer MCF-7 cells proliferation
and to explore its possible mechanism.
Methods: Sulforhodamine B (SRB) assay was used to test the proliferation rate of MCF-7 cells. Flow
cytometry was utilized to determine cell cycle. RT-qPCR and western blot were employed to evaluate
the expressions of proliferation-related factors in mRNA and protein levels.
Results: According to SRB assay and flow cytometric analysis, low dose of acacetin from 10-3 to 1µM
promoted the MCF-7 cells proliferation in a dose-dependent and time-dependent manner. Moreover,
the expressions of cell cycle-related molecules, ERK1/2 and PI3K/AKT were increased after treatment
with acacetin, while the increases were effectively reversed by ER antagonist ICI 182,780. Further
studies showed that acacetin notably induced increasing mRNA and proteins levels of ERα, which
were strongly reversed by ERα antagonist MPP.
Conclusion: Low dose of acacetin from 10-3
µM to µM promoted the proliferation of MCF-7 cells
through the ERK/PI3K/AKT pathway and its downstream cyclin signaling. And ERα is mainly responsible
for acacetin promoting proliferation in MCF-7 cells.