Abstract
BackgroundThe 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.MethodsCell 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.ResultsAfter 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.ConclusionsOur 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.
Highlights
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
Inhibition of proliferation after 7BIO treatment 14 thyroid cell lines derived from follicular, papillary and anaplastic thyroid carcinomas were treated with increasing concentrations of 7BIO or vehicle for 48 h
We found IC50 values for 7BIO in a similar range for all cell lines examined independent of the subtype of thyroid carcinoma they were derived from (1.54–4.83 μM)
Summary
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. We investigated the effect of 7BIO on thyroid carcinoma cell lines of different histological origins and characterized the type of cell death induction by 7BIO. Cell death can be induced by different pathways that are regulated by different intracellular signalling cascades, i.e., mainly apoptosis, necrosis, necroptosis, and autophagy [Review: 14]. As the third type of cell death mechanism, describes the process of self-digestion of cellular components by the cells [Review: 21]. During this regulated cellular process organelles and cell components are degraded and recycled and in addition to inducing death in single cells, it is a survival mechanism for the whole cell population in situations like starvation or cellular damage [22]
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