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

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 adva...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2017-07, Vol.143 (7), p.1143-1154
Main Authors: Schwertheim, Suzan, Wein, Frederik, Lennartz, Klaus, Worm, Karl, Schmid, Kurt Werner, Sheu-Grabellus, Sien-Yi
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Blotting, Western
Cancer Research
Cell Cycle Checkpoints - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Curcumin - pharmacology
Enzyme-Linked Immunosorbent Assay
Gene Expression Profiling
Hematology
Humans
Internal Medicine
Medicine
Medicine & Public Health
NF-kappa B - antagonists & inhibitors
Oncology
Original Article – Cancer Research
Real-Time Polymerase Chain Reaction
Thyroid Neoplasms - pathology
Transcriptome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-017-2380-z