title: Viscum Album Var Hot Water Extract Mediates Anti-cancer Effects through G1 Phase Cell Cycle Arrest in SK-Hep1 Human Hepatocarcinoma cells.
abstract: Viscum album var (VAV) also known as mistletoe, has long been categorized as a traditional herbal medicine in Asia. In addition to its immunomodulating activities, mistletoe has also been used in the treatment of chronic hepatic disorders in China and Korea. There are numerous reports showing that VAV possesses anti-cancer effects, however influence on human hepatocarcinoma has never been elucidated. In the present study, hot water extracts of VAV was evaluated for its potential anti-cancer effect in vitro. SK-Hep1 cells were treated with VAV (50-400 ug/ml) for both 24 and 48 hours then cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry analysis was used to measure the proportion of SK-Hep1 in the different stages of cell cycle. RT-PCR and Western blot analysis were conducted to measure expression of cell cycle arrest related genes and proteins respectively. VAV dose dependently inhibited the proliferation of SK-Hep1 cells without any cytotoxicity with normal Chang liver cell (CCL-13). Flow cytometry analysis showed that VAV extract inhibited the cell cycle of SK-Hep1 cells via G1 phase arrest. RT-PCR and Western blot analysis both revealed that cyclin dependent kinase 2 (Cdk2) and cyclin D1 gene expression were significantly down regulated while p21 was upregulated dose dependently by VAV treatment. Combined down regulation of Cdk2, Cyclin D1 and up regulation of p21 can result in cell death. These results indicate that VAV showed evidence of anti-cancer activity through G1 phase cell cycle arrest in SK-Hep1 cells.
authors.affiliation: Department of Animal Life And Environmental Science, Molecular Biology And Biotechnology, Hankyong National University, Anseong-Si, Korea E-mail : sghwang@hknu.ac.kr.
authors.forename: Joseph Flores
authors.initials: JF
authors.lastname: dela Cruz
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Wenchie Marie Lara
authors.initials: WM
authors.lastname: Lumbera
authors.forename: Seong Gu
authors.initials: SG
authors.lastname: Hwang
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D028182:Viscum album; D014867:Water
chemical_list: D016588:Anticarcinogenic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; D014867:Water; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2