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Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells

Abstract

Purpose

The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin’s molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer.

Methods

Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits.

Results

Treatment with 50 μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase.

Conclusions

Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.

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Acknowledgements

No funding was received specifically for this study.

Author information

Correspondence to Suzan Schwertheim.

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Conflict of interest

The authors declare that they have no conflict of interest. No funding was received specifically for this study.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

No human participants were used in this study.

Additional information

K. W. Schmid and S.-Y. Sheu-Grabellus contributed equally to this work.

An erratum to this article is available at http://dx.doi.org/10.1007/s00432-017-2403-9.

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Schwertheim, S., Wein, F., Lennartz, K. et al. Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells. J Cancer Res Clin Oncol 143, 1143–1154 (2017). https://doi.org/10.1007/s00432-017-2380-z

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Keywords

  • Curcumin
  • NF-κB
  • G2/M arrest 
  • Thyroid cancer