title: Polyphenolic extract isolated from Korean Lonicera japonica Thunb. induce G2/M cell cycle arrest and apoptosis in HepG2 cells: involvements of PI3K/Akt and MAPKs.
abstract: Lonicera japonica Thunb. (L. japonica T.) has been used in Korean traditional medicine for long time because of its anti-cancer and hepatic protective effect. In this study, we investigated polyphenolic extract in L. japonica T. using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) and its anti-cancer effect on hepatocarcinoma cells. Human HepG2 cell line was treated with various concentrations of polyphenolic extract. Apoptosis was detective by cell morphology, cell cycle analysis and immunoblot analysis. Polyphenolic extract inhibited cell proliferation at 48h in a dose-dependent manner. Polyphenolic extract affected HepG2 cell viability by inhibiting cell cycle progression at the G2/M transition and inducing apoptosis. Polyphenolic extract also decreased the expression of CDK1, CDC25C, cyclin B1, pro-caspases-3 and -9 and poly ADP ribose polymerase, and affected the levels of mitochondrial apoptotic-related proteins. The phosphorylation of extracellular signal-related kinase ½ (ERK 1/2), c-Jun N-terminal kinase (JNK), and p-38 mitogen-activated protein kinases (MAPKs) were increased in HepG2 cells treated with polyphenolic extract, whereas Akt was dephosphorylated. These results indicate that inhibition of PI3K/Akt and activation of MAPKs are pivotal in G2/M cell cycle arrest and apoptosis of human hepatocarcinoma cells mediated by polyphenolic extract.
authors.affiliation: Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Park
authors.forename: Do-Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Sang-Rim
authors.initials: SR
authors.lastname: Kang
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Gon-Sup
authors.initials: GS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D031239:Lonicera / Q000737:chemistry*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D059808:Polyphenols; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases