title: Ethanol extract of Kalopanax septemlobus leaf inhibits HepG2 human hepatocellular carcinoma cell proliferation via inducing cell cycle arrest at G1 phase.
abstract: 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.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Research and Development of Resources, Gurye-gun Agricultural Center, Gurye-gun, Jeonam, 054-805, Republic of Korea; Wild Flower Institute, Gurye-gun, Jeonam, 054-805, Republic of Korea.
authors.forename: Ji-Suk
authors.initials: JS
authors.lastname: Jeong
authors.affiliation: Anti-Aging Research Center, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Food Science & Biotechnology, College of Engineering, Kyungsung University, Busan, 608-736, Republic of Korea.
authors.forename: Sung Ok
authors.initials: SO
authors.lastname: Kim
authors.affiliation: Wild Flower Institute, Gurye-gun, Jeonam, 054-805, Republic of Korea.
authors.forename: Yong-Joo
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-714, Republic of Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Anti-Aging Research Center, Dongeui University, Busan, 614-714, Republic of Korea; Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-714, Republic of Korea. Electronic address: choiyh@deu.ac.kr.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
keywords: CDK inhibitor; G(1) cell cycle arrest; Hepatocellular carcinoma; Kalopanax septemlobus; pRB