Abstract | PURPOSE: Patients with advanced and metastasized medullary thyroid carcinoma are difficult to treat since tumor cells do not respond to chemotherapeutic treatment and external radiation. Direct induction of cell death is a new therapeutic approach to therapy-resistant tumor cells. In this study we analyzed the effect of the indirubin-derivative 7BIO and the BH3 mimetic drugs ABT-737 and GX15-070 on cell death induction of TT medullary thyroid carcinoma cells. METHODS: RESULTS: Incubation with all 3 drugs efficiently decreased the number of viable TT cells with IC50 values of 4.1 µM (7BIO), 0.19 µM (ABT-737) and 0.23 µM (GX15-070). The BH3 mimetic ABT-737 caused an apoptotic cell death with caspase activation as expected, while 7BIO- and GX15-070-treatment led to a mixed kind of cell death, where caspase activation was detected but had no effect on viability of TT cells. LC3 conversion as a biochemical marker of autophagic cell death was observed after GX15-070 treatment while LDH release pointed to involvement of necrosis after treatment with all 3 drugs. CONCLUSION: The BH3 mimetic drugs ABT-737 and GX15-070 efficiently killed TT medullary thyroid carcinoma cells with low IC50 values, while the indirubin-derivative 7BIO was also effective but with a higher IC50 value. Although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells.
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Authors | M Broecker-Preuss, N Becher-Boveleth, K Mann |
Journal | Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
(Exp Clin Endocrinol Diabetes)
Vol. 124
Issue 5
Pg. 324-30
(May 2016)
ISSN: 1439-3646 [Electronic] Germany |
PMID | 26849668
(Publication Type: Journal Article)
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Copyright | © Georg Thieme Verlag KG Stuttgart · New York. |
Chemical References |
- ABT-737
- BH3 Interacting Domain Death Agonist Protein
- Biphenyl Compounds
- Indoles
- Nitrophenols
- Piperazines
- Protein Kinase Inhibitors
- Pyrroles
- Sulfonamides
- obatoclax
- indirubin
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Topics |
- BH3 Interacting Domain Death Agonist Protein
- Biphenyl Compounds
(pharmacology)
- Carcinoma, Neuroendocrine
(drug therapy)
- Cell Death
(drug effects)
- Cell Line, Tumor
- Humans
- Indoles
(pharmacology)
- Molecular Mimicry
- Nitrophenols
(pharmacology)
- Piperazines
(pharmacology)
- Protein Kinase Inhibitors
(pharmacology)
- Pyrroles
(pharmacology)
- Sulfonamides
(pharmacology)
- Thyroid Neoplasms
(drug therapy)
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