title: Cellular Effect of Curcumin and Citral Combination on Breast Cancer Cells: Induction of Apoptosis and Cell Cycle Arrest.
abstract: OBJECTIVE
  The unmanageable side effects caused by current chemotherapy regimens to treat cancer are an unresolved problem. Although many phytonutrients are useful as chemoprevention without side effects, their effects are slower and smaller than conventional chemotherapy. In the present work, we examined the cumulative effect of two phytonutrients, curcumin and citral, on breast cancer cell lines and compared their effect with the known chemotherapy regimen of cyclophosphamide, methotrexate, and 5-fluorouracil.
  
  
  METHODS
  Using cultured breast cancer and normal epithelial cells, the cytotoxic and apoptotic effect of curcumin and citral was evaluated in vitro. The synergistic effect of curcumin and citral was calculated by a combination index study using the method by Chou and Talalay. Cell death pathways and mechanisms were analyzed by measuring intracellular reactive oxygen species (ROS) and apoptotic protein levels.
  
  
  RESULTS
  Curcumin and citral caused dose and time dependent cell death and showed a synergistic effect at effective concentration EC50 and above concentrations in breast cancer cells without disturbing normal breast epithelial cells. With combination curcumin and citral treatment, apoptosis induction and cell cycle arrest at G0/G1 phase in breast cancer cells were observed. Curcumin and citral generated ROS and activated p53 and poly (ADP-ribose) polymerase-1 mediated apoptotic pathways.
  
  
  CONCLUSIONS
  The results of this study suggest that curcumin and citral in combination may be a useful therapeutic intervention for breast cancer.
authors.affiliation: Biochemistry Division, B. R. Doshi School of Biosciences, Sardar Patel University, Vallabh Vidyanagar, India.
authors.forename: Pinaki B
authors.initials: PB
authors.lastname: Patel
authors.affiliation: Biochemistry Division, B. R. Doshi School of Biosciences, Sardar Patel University, Vallabh Vidyanagar, India.
authors.forename: Vasudev R
authors.initials: VR
authors.lastname: Thakkar
authors.affiliation: P. D. Patel Institute of Applied Science, Charotar University of Science and Technology (CHARUSAT), Changa, India.
authors.forename: Jagdish S
authors.initials: JS
authors.lastname: Patel
keywords: Apoptosis; Breast cancer cell line; Cell cycle checkpoints; Citral; Curcumin