title: Erucin and benzyl isothiocyanate suppress growth of late stage primary human ovarian carcinoma cells and telomerase activity in vitro.
abstract: In the present study we analysed the effects of isothiocyanates (ITCs)--plant-derived sulphur-containing constituents known for their potential chemotherapeutic activity--on growth inhibition and programmed death in primary ovarian carcinoma cells from ascites of human patients. Twenty-four hour exposure of carcinoma cells to 5-50 μM erucin or benzyl ITC led to a concentration-dependent viability loss, as determined by erytrosin B cell staining. This concurred with an increase in internucleosomal DNA fragmentation, mitochondrial membrane depolarization and downregulation of Akt as indicator for apoptosis induction. Cell accumulation at the G2/M phase was evident after 48 h of erucin treatment. Telomerase, a selective target of cancer cells, was suppressed by erucin. Although pre-treatment of cells with the thiol antioxidant N-acetylcysteine could completely prevent initialization of the apoptotic process, it failed to abolish ITC-mediated telomerase suppression. Taken together, in our study, ITC exerted comparable cytotoxic efficacy against primary ovarian cancer cells as reported for corresponding cell lines. The clinical significance of this observation should be addressed in future studies and the role of telomerase further investigated.
authors.affiliation: Department of Environmental Health Sciences, University Medical Center Freiburg, Breisacher Strasse 115b, 79106 Freiburg, Germany. evelyn.lamy@uniklinik-freiburg.de
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lamy
authors.forename: Dewi
authors.initials: D
authors.lastname: Oey
authors.forename: Florian
authors.initials: F
authors.lastname: Eißmann
authors.forename: Corinna
authors.initials: C
authors.lastname: Herz
authors.forename: Karsten
authors.initials: K
authors.lastname: Münstedt
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Tinneberg
authors.forename: Volker
authors.initials: V
authors.lastname: Mersch-Sundermann
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival; D053938:DNA Fragmentation; D015536:Down-Regulation; D005260:Female; D016195:G2 Phase; D006801:Humans; D017879:Isothiocyanates / Q000627:therapeutic use*; D051336:Mitochondrial Membranes / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000627:therapeutic use*; D019098:Telomerase / Q000187:drug effects*; D013861:Thiocyanates / Q000627:therapeutic use*
chemical_list: D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D013440:Sulfides; D013861:Thiocyanates; C031403:benzyl isothiocyanate; C073539:erucin; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase; D000111:Acetylcysteine