Aspidin BB, an effective
phloroglucinol derivative from Dryopteris fragrans (L.) Schott, has been previously reported to exert high
biological activities. In this study, we analyzed the underlying mechanisms of
aspidin BB on human
ovarian cancer cell line, HO-8910.
Aspidin BB significantly inhibited HO-8910 cell proliferation in a dose- and time-dependent manner. The IC50 values were 15.02, 25.79 and 68.81μM after 72, 48 and 24h treatment, respectively. Meanwhile,
aspidin BB markedly induced apoptosis evidenced by characteristic apoptotic morphological changes, nuclear DNA fragmentation,
annexin V-FITC/
propidium iodide (PI) double staining and S peak. Western blot analysis showed that
aspidin BB suppressed Bcl-2 expression and enhanced Bax expression to desintegrate the outer mitochondrial membrane, then caused
cytochrome c release which led to the activation of effector
caspase-3, and further cleaved the
poly ADP-ribose polymerase (PARP) in the nucleus, finally induced cell apoptosis. Furthermore,
aspidin BB provoked S phase arrest in HO-8910 cells with up-regulation of pRb, E2F1, CDK2,
cyclin E and
cyclin A proteins. Taken together, these findings support the conclusion that
aspidin BB exhibits cytotoxicity towards human
ovarian cancer HO-8910 cells through induction of apoptosis via mitochondrial pathway and arresting cell cycle progression in S phase.