title: Synergistic combinations of tanshinone IIA and trans-resveratrol toward cisplatin-comparable cytotoxicity in HepG2 human hepatocellular carcinoma cells.
abstract: OBJECTIVE
  To determine the combinative effects of tanshinone IIA (Tan IIA) and trans-resveratrol (Resv) on cytotoxicity, apoptosis, cell-cycle arrest and DNA fragmentation in HepG2 human liver cancer cells.
  
  
  METHODS
  Cytotoxicity was detected by the cell proliferation and cytotoxicity WST-1 assay. Cell-cycle arrest and apoptosis were determined using flow cytometry analysis. DNA fragments were separated by gel electrophoresis.
  
  
  RESULTS
  Tan IIA and Resv at mixture ratios of 1/2:1/2 and 1/3:2/3 exerted synergistic cytotoxicity comparable to that of cisplatin. Elevated proportions of sub-G1 and apoptotic cells were respectively found in the combinative treatments in comparison with hypothetic values of additive effects. Moreover, a more intensive pattern of apoptotic DNA fragmentation was visualized in combined treatments than in individual ones.
  
  
  CONCLUSIONS
  Combining Tan IIA and Resv causes synergistic cisplatin-comparable, cytotoxicity and robustly induces apoptosis, sub-G1 cell cycle arrest and DNA fragmentation. This study provides evidence supporting further pre-clinical investigations of the combinational synergism.
authors.affiliation: Department of Agronomy, National Taiwan University, Taipei, Taiwan, R.O.C Division of Crop Improvement, Hualien District Agricultural Research and Extension Station, Council of Agriculture, Hualien County, Taiwan, R.O.C.
authors.forename: Tung-Wu
authors.initials: TW
authors.lastname: Chang
authors.affiliation: Institute of Medical Sciences, Tzu-Chi University, Hualien City, Taiwan, R.O.C.
authors.forename: Chueh-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien City, Taiwan, R.O.C tzeng@mail.tcu.edu.tw tzeng@gms.tcu.edu.tw lurhs@ntu.edu.tw.
authors.forename: Yin-Jeh
authors.initials: YJ
authors.lastname: Tzeng
authors.affiliation: Department of Agronomy, National Taiwan University, Taipei, Taiwan, R.O.C tzeng@mail.tcu.edu.tw tzeng@gms.tcu.edu.tw lurhs@ntu.edu.tw.
authors.forename: Huu-Sheng
authors.initials: HS
authors.lastname: Lur
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D053938:DNA Fragmentation / Q000187:drug effects; D004357:Drug Synergism; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D045784:Abietanes; D013267:Stilbenes; C021751:tanshinone; D002945:Cisplatin; D000077185:Resveratrol
keywords: Tanshinone IIA; apoptosis; cell cycle arrest; cisplatin; synergistic combination; trans-resveratrol