Ampelopsin (
AMP), a plant
flavonoid, has been reported to inhibit cell growth and/or induce apoptosis in various types of
tumor. The aim of the present study was to assess the apoptosis-inducing activity of
AMP in A549 human
lung adenocarcinoma epithelial cells and the associated underlying mechanism. A549 cells were incubated with different concentrations of
AMP in culture medium. Cell growth and apoptosis were evaluated by MTT assay and
Annexin V/
propidium iodide double staining and flow cytometry, respectively. In addition, western blotting and reverse transcription quantitative polymerase chain reaction analysis were used to examine the time-dependent changes in
protein expression. Certain changes in apoptotic
protein expression were detected following exposure to
AMP, including
X-linked inhibitor of apoptosis protein release, reduced
B-cell lymphoma 2, myeloid cell
leukemia 1 and
survivin expression levels, increased
Bcl-2-associated X protein expression levels and cleaved-
poly ADP ribose polymerase expression. The results revealed that
AMP was a potent inhibitor of A549 cell proliferation. The c-Myc/
S-phase kinase-associated protein 2 (Skp2) and
histone deacetylase (HDAC)1/2 pathways were found to exert an important role in
AMP-induced A549 cell apoptosis, as increased levels of c-Myc
mRNA and reduced levels of c-Myc/Skp2 and HDAC1 and 2
proteins following
AMP treatment were observed. The levels of F-box and WD repeat-containing
protein 7α (Fbw7α), Fbw7β, Fbw7γ, phosphorylated-(p-)c-Myc (Thr58) and
glycogen synthase kinase 3β (GSK3β)
proteins involved in c-Myc
ubiquitin-dependent degradation were also analyzed. Following exposure to
AMP, the expression levels of Fbw7α, Fbw7γ and GSK3β were reduced and p-c-Myc (Thr58) expression levels were increased. The results suggest that
AMP exerts an anticancer effect, which is associated with the degradation of c-Myc, Skp2 and HDAC1 and 2. The ability of
AMP to induce apoptosis independently of Fbwα and Fbw7γ suggests a possible use in
drug-resistant
cancer associated with Fbw7 deficiency. Understanding the exact underlying mechanism requires further investigation of the association between c-Myc and Fbw7α/γ reversal, and analysis of whether Thr58 phosphorylation of c-Myc is dependent on GSK3β.