title: Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells.
abstract: BACKGROUND
  Doxorubicin is a chemotherapy agent used in non-Hodgkin's lymphoma but side effects limit its use. Citral is a mixture of neral and geranial found in essential oils of lemon grass.
  
  
  OBJECTIVE
  We evaluated the activity of citral, doxorubicin, and combination on cytotoxicity, apoptosis, and anti-proliferative effects using human lymphoma Ramos cells.
  
  
  METHODS
  Cells were treated with doxorubicin alone or in combination with citral (10, 20, and 40 μM). Cytotoxic and apoptosis studies were done after 24 and 18 h incubations, respectively. Cytotoxic effects of citral on normal human peripheral blood mononuclear cells (PBMCs) were also investigated for its safety. Changes in the expression of BCL-2 family genes were analyzed by quantitative RT-PCR.
  
  
  RESULTS
  Citral had cytotoxicity on cells with an IC50 value of 77.19 ± 4.95 µM. Citral at concentrations of 10, 20, and 40 µM additively increased the cytotoxic and apoptotic effects of doxorubicin, leading to decreased IC50 (µM) of the drug from 2.50 ± 0.01 to 2.16 ± 0.03, 1.90 ± 0.04, and 1.23 ± 0.04, respectively. Enhanced cytotoxicity was not observed in normal human PBMCs. Citral (40 µM) in combination with doxorubicin (1.5 µM) increased the expression of pro-apoptotic protein BAK but significantly decreased the expression of anti-apoptotic protein BCL-XL to 5.26-fold compared with doxorubicin-treated cells. It did not change the anti-proliferative activity of drug.
  
  
  CONCLUSIONS
  Citral potentiated cytotoxicity of doxorubicin by increasing apoptotic effects. We conclude that citral may have beneficial effects in patients with B cell lymphoma treated with chemotherapy.
authors.affiliation: Interdisciplinary Program of Pharmacology, Graduate School, Chulalongkorn University , Bangkok , Thailand and.
authors.forename: Darinee
authors.initials: D
authors.lastname: Dangkong
authors.forename: Wacharee
authors.initials: W
authors.lastname: Limpanasithikul
mesh_terms: D000080462:Acyclic Monoterpenes; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics
chemical_list: D000080462:Acyclic Monoterpenes; D000903:Antibiotics, Antineoplastic; D039821:Monoterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D004317:Doxorubicin; C007076:citral
keywords: Anticancer; Burkitt's lymphoma; anti-proliferative; apoptosis; chemopotentiation; human peripheral blood mononuclear cells; lemon grass; potentiating agent