title: Biological activity of terpene compounds produced by biotechnological methods.
abstract: BACKGROUND
  Biotransformation systems are profitable tools for structural modification of bioactive natural compounds into valuable biologically active terpenoids.
  
  
  OBJECTIVE
  This study determines the biological effect of (R)-(+)-limonene and (-)-α-pinene, and their oxygenated derivatives, (a) perillyl alcohol and (S)-(+)- and (R)-(-)-carvone enantiomers and (b) linalool, trans-verbenol and verbenone, respectively, on human colon tumour cells and normal colonic epithelium.
  
  
  METHODS
  Biotransformation procedures and in vitro cell culture tests were used in this work. Cells were incubated for 24 h with terpenes at concentrations of 5-500 μg/mL for NR, MTT, DPPH, and NO assays. IL-6 was determined by ELISA with/without 2 h pre-activation with 10 μg/mL LPS.
  
  
  RESULTS
  trans-Verbenol and perillyl alcohol, obtained via biotransformation, produced in vitro effect against tumour cells at lower concentrations (IC50 value = 77.8 and 98.8 μg/mL, respectively) than their monoterpene precursors, (R)-(+)-limonene (IC50 value = 171.4 μg/mL) and (-)-α-pinene (IC50 value = 206.3 μg/mL). They also showed lower cytotoxicity against normal cells (IC50 > 500 and > 200 μg/mL, respectively). (S)-(+)-Carvone was 59.4% and 27.1% more toxic to tumour and normal cells, respectively, than the (R)-(-)-enantiomer. (R)-(+)-limonene derivatives decreased IL-6 production from normal cells in media with or without LPS (30.2% and 13.9%, respectively), while (-)-α-pinene derivatives induced IL-6 (verbenone had the strongest effect, 60.2% and 29.1% above control, respectively). None of the terpenes had antioxidative activity below 500 μg/mL.
  
  
  CONCLUSIONS
  Bioactivity against tumour cells decreased in the following order: alcohols > ketones > hydrocarbons. (R)-(+)-limonene, (-)-α-pinene, and their derivatives expressed diverse activity towards normal and tumour cells with noticeable enantiomeric differences.
authors.affiliation: a Department of Virology and Immunology , Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland ;
authors.forename: Roman
authors.initials: R
authors.lastname: Paduch
authors.affiliation: b Department of Industrial Microbiology , Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Trytek
authors.affiliation: a Department of Virology and Immunology , Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland ;
authors.forename: Sylwia K
authors.initials: SK
authors.lastname: Król
authors.affiliation: a Department of Virology and Immunology , Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland ;
authors.forename: Joanna
authors.initials: J
authors.lastname: Kud
authors.affiliation: a Department of Virology and Immunology , Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland ;
authors.forename: Maciej
authors.initials: M
authors.lastname: Frant
authors.affiliation: a Department of Virology and Immunology , Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland ;
authors.forename: Martyna
authors.initials: M
authors.lastname: Kandefer-Szerszeń
authors.affiliation: b Department of Industrial Microbiology , Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University , Lublin , Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Fiedurek
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001709:Biotechnology / Q000379:methods*; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002912:Chrysosporium / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000473:pathology; D055808:Drug Discovery / Q000379:methods*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D020094:Mortierella / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010851:Picrates / Q000737:chemistry; D013729:Terpenes / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D010851:Picrates; D013729:Terpenes; D009569:Nitric Oxide; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: Colon cancer; essential oils; free radicals scavenging; terpenes; toxicity