Phytoestrogens have been demonstrated to inhibit
tumor induction; however, their molecular mechanisms of action have remained elusive. The present study aimed to investigate the effects of a
phytoestrogen,
apigenin, on proliferation and apoptosis of the
human epidermal growth factor receptor 2 (HER2)-expressing
breast cancer cell line SKBR3. Proliferation assay, MTT assay, fluorescence-activated cell sorting analysis, western blot analysis, immunocytochemistry, reverse transcription-polymerase chain reaction and ELISA assay were used in the present study. The results of the present study indicated that
apigenin inhibited the proliferation of SKBR3 cells in a dose-and time-dependent manner. This inhibition of growth was accompanied by an increase in the sub-G0/G1 apoptotic population. Furthermore,
apigenin enhanced the expression levels of cleaved
caspase-8 and -3, and induced the cleavage of
poly(adenosine diphosphate ribose) polymerase in SKBR3 cells, confirming that
apigenin promotes apoptosis via a
caspase-dependent pathway.
Apigenin additionally reduced the expression of phosphorylated (p)-
janus kinase 2 and p-
signal transducer and activator of transcription 3 (STAT3), inhibited CoCl2-induced
vascular endothelial growth factor (
VEGF) secretion and decreased the nuclear localization of STAT3. The STAT3 inhibitor S31-201 decreased the cellular proliferation rate and reduced the expression of p-STAT3 and
VEGF. Therefore, these results suggested that
apigenin induced apoptosis via the inhibition of STAT3 signaling in SKBR3 cells. In conclusion, the results of the present study indicated that
apigenin may be a potentially useful compound for the prevention or treatment of HER2-overexpressing
breast cancer.