Aspidin PB, a
phloroglucinol derivative isolated from Dryopteris fragrans (L.) Schott, has been previously reported to exert high
biological activities. In the present study, we analyzed the apoptotic mechanisms of
aspidin PB on human
hepatoma cell line, HepG2. Initially,
aspidin PB was shown to inhibit the growth of HepG2 cells in a time and dose-dependent manner.
After treatment with
aspidin PB for 72 h, 48 h and 24 h using MTT assay, the IC(50) values were 10.59 μM, 20.86 μM and 46.59 μM, respectively.
Aspidin PB was capable to induce apoptosis, as measured by mitochondrial membrane potential (ΔΨm),
acridine orange (AO) staining and
propidium iodide (PI)/
annexin V-FITC double staining. To further explore the signaling pathway of
aspidin PB-mediated apoptosis, we examined PI3K/Akt related
proteins. Western blot analysis revealed that
aspidin PB inhibited PI3K expression, phosphorylation of Ser473 Akt and Ser9 GSK3β followed by up-regulation of nonsteroidal anti-inflammatory drugs activated gene-1 (NAG-1) expression. Similarly, the effects of
aspidin PB on PI3K, Akt, GSK3β, NAG-1 expression were abolished by treatment with the PI3K inhibitor,
wortmannin. Taken together, our data suggested that the PI3K/Akt/GSK3β signal pathway may represent one of the major mechanisms of the effects of
aspidin PB on human hepatocarcinoma cells.