چکیده (انگلیسی):

Objective: To investigate the effects of an ethanol extract of Kalopanax septemlobus
(Thunb.) Koidz. leaf (EEKS) on cell proliferation in human hepatocellular carcinoma
cells and its mechanisms of action.
Methods: Cells were treated with EEKS and subsequently analyzed for cell proliferation
and flow cytometry analysis. Expressions of cell cycle regulators were determined by
reverse transcriptase polymerase chain reaction analysis and Western blotting, and activation
of cyclin-associated kinases studied using kinase assays.
Results: The EEKS suppressed cell proliferation in both HepG2 and Hep3B cells, but
showed a more sensitive anti-proliferative activity in HepG2 cells. Flow cytometry
analysis revealed an association between the growth inhibitory effect of EEKS and with
G1 phase cell cycle arrest in HepG2 cells, along with the dephosphorylation of retinoblastoma
protein (pRB) and enhanced binding of pRB with the E2F transcription factor
family proteins. Treatment with EEKS also increased the expression of cyclin-dependent
kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, without any noticeable
changes in G1 cyclins and CDKs (except for a slight decrease in CDK4). Treatment of
HepG2 cells with EEKS also increased the binding of p21 and p27 with CDK4 and
CDK6, which was paralleled by a marked decrease in the cyclin D- and cyclin E-associated
kinase activities.
Conclusions: Overall, our findings suggest that EEKS may be an effective treatment for
liver cancer through suppression of cancer cell proliferation via G1 cell cycle arrest.
Further studies are required to identify the active compounds in EEKS.