Ethanol extract of Kalopanax septemlobus leaf inhibits HepG2 human hepatocellular carcinoma cell proliferation via inducing cell cycle arrest at G₁ phase

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• 作者：Cheol Park¹ ; ^# ; Ji-Suk Jeong² ; ³ ; ^# ; Jin-Woo Jeong⁴ ; Sung Ok Kim⁵ ; Yong-Joo Kim³ ; Gi-Young Kim⁶ ; Su-Hyun Hong⁷ ; Yung Hyun Choi⁴ ; ⁷ ; ^{choiyh@deu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Kalopanax septemlobus ; Hepatocellular carcinoma ; G1 cell cycle arrest ; CDK inhibitor ; pRB
• 刊名：Asian Pacific Journal of Tropical Medicine
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：9
• 期：4
• 页码：344-350
• 全文大小：1124 K

文摘

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.