title: Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells.
abstract: Isothiocyanates are constituents of cruciferous vegetables which have been associated with reduced cancer risk partially through their ability to induce apoptosis in malignant cells including melanoma.
  
  
  
  We have utilized human malignant melanoma (A375), epidermoid carcinoma (A431) and immortalized keratinocyte (HaCaT) cells exposed to various isothiocyanates, under different experimental conditions.
  
  
  
  An experimental in vitro model utilizing low isothiocyanate concentrations (0.1-5 μM for 48 h with all treatments being refreshed after 24h) was shown to be (i) most efficient in exerting an anti-cancer effect when compared to higher concentrations (5-100 μM for 24 or 48 h added as a single bolus) and (ii) specific to A375 cells while A431 and HaCaT cells remained unaffected. Such effect involved the activation of several caspases including (iii) initiator caspases 8, 9, 4 (indicating the involvement of intrinsic, extrinsic and endoplasmic reticulum-based pathways) and (iv) effector caspases 3, 7 and 6.
  
  
  
  Utilization of low isothiocyanate concentrations (under the conditions described herein) exerts an anti-cancer effect specific to human malignant melanoma cells thus providing a therapeutic basis for their utilization in management of the disease.
authors.affiliation: School of Life Sciences, Heriot Watt University, Edinburgh, Scotland, U.K.
authors.forename: Theodora
authors.initials: T
authors.lastname: Mantso
authors.affiliation: School of Life Sciences, Heriot Watt University, Edinburgh, Scotland, U.K.
authors.forename: Aristeidis P
authors.initials: AP
authors.lastname: Sfakianos
authors.affiliation: School of Life Sciences, Heriot Watt University, Edinburgh, Scotland, U.K.
authors.forename: Aithne
authors.initials: A
authors.lastname: Atkinson
authors.affiliation: Department of Molecular & Cell Biology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anestopoulos
authors.affiliation: Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, U.K.
authors.forename: Melina
authors.initials: M
authors.lastname: Mitsiogianni
authors.affiliation: Second Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Botaitis
authors.affiliation: Second Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Sebachedin
authors.initials: S
authors.lastname: Perente
authors.affiliation: Second Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Simopoulos
authors.affiliation: Department of Molecular & Cell Biology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Vasileiadis
authors.affiliation: Redox Biology Centre, University of Nebraska, Lincoln, NE, U.S.A.|School of Veterinary Medicine & Biomedical Sciences, University of Nebraska, Lincoln, NE, U.S.A.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Franco
authors.affiliation: Department of Molecular & Cell Biology, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Aglaia
authors.initials: A
authors.lastname: Pappa
authors.affiliation: School of Life Sciences, Heriot Watt University, Edinburgh, Scotland, U.K. m.panagiotidis@northumbria.ac.uk.|Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, U.K.
authors.forename: Mihalis I
authors.initials: MI
authors.lastname: Panayiotidis
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology*; D008545:Melanoma / Q000473:pathology*
chemical_list: D017879:Isothiocyanates; C037152:isothiocyanic acid
keywords: Isothiocyanates; apoptosis; benzyl isothiocyanate; malignant melanoma; phenethyl isothiocyanate; sulforaphane