title: Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells.
abstract: BACKGROUND
  Gamma-tocotrienol (GTT), an isomer of vitamin E and hydroxy-chavicol (HC), a major bioactive compound in Piper betle, has been reported to possess anti-carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi-drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bioactives in cancer treatment.
  
  
  METHODS
  In this study, we investigated the interaction of GTT and HC and its mode of cell death on glioma cell lines. GTT or HC alone and in combination were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) by [3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)- 2H- tetrazolium, inner salt] MTS assay. The interactions of each combination were evaluated by using the combination index (CI) obtained from an isobologram.
  
  
  RESULTS
  Individually, GTT or HC displayed mild growth inhibitory effects against glioma cancer cell lines at concentration values ranging from 42-100 μg/ml and 75-119 μg/ml respectively. However, the combination of sub-lethal doses of GTT + HC dramatically enhanced the inhibition of glioma cancer cell proliferation and exhibited a strong synergistic effect on 1321N1 with CI of 0.55, and CI = 0.54 for SW1783. While in LN18 cells, moderate synergistic interaction of GTT + HC was observed with CI value of 0.73. Exposure of grade II, III and IV cells to combined treatments for 24 hours led to increased apoptosis as determined by annexin-V FITC/PI staining and caspase-3 apoptosis assay, showing caspase-3 activation of 27%, 7.1% and 79% respectively.
  
  
  CONCLUSIONS
  In conclusion, combined treatments with sub-effective doses of GTT and HC resulted in synergistic inhibition of cell proliferation through the induction of apoptosis of human glioma cells in vitro.
authors: Amirah
authors: A
authors: Abdul Rahman
authors: A Rahman A
authors: AR
authors: Jamal
authors: Roslan
authors: R
authors: Harun
authors: Norfilza
authors: N
authors: Mohd Mokhtar
authors: UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Jalan Ya'acob, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia. zurina@medic.ukm.my.
authors: Wan Zurinah
authors: WZ
authors: Wan Ngah
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005054:Eugenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002839:Chromans; C051268:2-hydroxychavicol; D014810:Vitamin E; D005054:Eugenol; C013649:plastochromanol 8