title: Induction of atypical cell death in thyroid carcinoma cells by the indirubin derivative 7-bromoindirubin-3'-oxime (7BIO).
abstract: BACKGROUND
  The indirubin derivative 7-bromoindirubin-3'-oxime (7BIO) has already shown anticancer properties by causing cell death in some tumour cell lines and may be a new therapeutic option for treatment-resistant tumour cells. Since dedifferentiated and anaplastic thyroid carcinomas do not take up radioiodine and are insensitive to chemotherapeutic treatment and external radiation, direct cell death induction in these tumour cells may be a promising approach. We thus investigated the effect of 7BIO on thyroid carcinoma cell lines of different histological origins and characterized the type of cell death induction by 7BIO.
  
  
  METHODS
  Cell viability was measured with MTT assay. Cell death was analysed by caspase 3/7 activity, lactate dehydrogenase liberation, caspase cleavage products, DNA fragmentation, cell cycle phase distribution and LC3B analysis.
  
  
  RESULTS
  After 7BIO treatment, cell viability was reduced in all 14 thyroid carcinoma cell lines investigated. Treated cells showed DNA fragmentation, cell cycle arrest and lactate dehydrogenase liberation but no LC3B cleavage. Caspase activation following 7BIO treatment was found in five of six cell lines investigated. Interestingly, inhibition of caspases had no effect on viability of the cells after 7BIO incubation.
  
  
  CONCLUSIONS
  Our results indicate that 7BIO efficiently killed dedifferentiated thyroid carcinoma cells. It induced a non-classical kind of cell death that was caspase-independent and includes DNA fragmentation. 7BIO and related indirubin components thus may have value as a new therapeutic option for dedifferentiated thyroid cancer irrespective of the exact target molecules and the kind of cell death they induce.
authors.affiliation: Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany ; Department of Clinical Chemistry, University Hospital Essen, Hufelandstr. 55, Essen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Broecker-Preuss
authors.affiliation: Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany ; Clinic of Nuclear Medicine, University Hospital Essen, Hufelandstr. 55, Essen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Becher-Boveleth
authors.affiliation: Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Gall
authors.affiliation: Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany ; Department of Clinical Chemistry, University Hospital Essen, Hufelandstr. 55, Essen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Rehmann
authors.affiliation: Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Schenke
authors.affiliation: Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany ; Center of Endocrinology Alter Hof München, Dienerstr. 12, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mann
keywords: 7BIO; Cell death; Dedifferentiated thyroid carcinoma; Indirubins