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2-methoxyestradiol ...
2-methoxyestradiol induces apoptosis in cultured human anaplastic thyroid carcinoma cells
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- Roswall, Pernilla (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Bu, Shizhong (author)
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- Rubin, Kristofer (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Landström, Maréne (author)
- Ludwiginstitutet för Cancerforskning
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- Heldin, Nils-Erik (author)
- Uppsala universitet,Institutionen för genetik och patologi
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(creator_code:org_t)
- 2006
- 2006
- English.
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In: Thyroid. - 1050-7256 .- 1557-9077. ; 16:2, s. 143-50
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Anaplastic thyroid carcinoma (ATC) is one of the most malignant tumors in humans, and currently there is no effective treatment. In the present study we investigated the effect of an endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), on the growth of human ATC cells. 2-ME treatment had a strong growth inhibitory effect on five human ATC cell lines (HTh7, HTh 74, HTh83, C643, and SW1736), but showed no effect on one cell line (KAT-4). Cell cycle analysis of the growth-inhibited cells showed that 2-ME induced a G2/M-arrest, followed by an increased fraction of cells in sub-G1. Analysis of internucleosomal DNA laddering as well as DNA fragmentation in a terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a high number of cells undergoing apoptosis after 2-ME treatment. An increased activation of caspase-3 and caspase-8 by 2-ME was observed, and inhibition of caspase-3 decreased the apoptotic effect. Addition of 2-ME increased activity of p38 mitogen-activated protein kinase (MAPK) in the sensitive HTh7 as well as the refractory KAT-4 cells, however, activation of stress-activated protein kinase/c-jun aminoterminal kinase (SAPK/JNK) was seen only in the HTh7 cells. Inhibitors of p38 MAPK and SAPK/JNK significantly attenuated the 2-ME effect. Taken together, our data demonstrate an antiproliferative and apoptotic effect of 2-ME on ATC cells involving activation of MAPKs.
Keyword
- Antineoplastic Agents/pharmacology
- Apoptosis
- Blotting; Western
- Carcinoma/*drug therapy/*metabolism/pathology
- Caspases/metabolism
- Cell Line; Tumor
- DNA Fragmentation
- Estradiol/*analogs & derivatives/pharmacology
- Flow Cytometry
- G1 Phase
- Humans
- In Situ Nick-End Labeling
- MAP Kinase Signaling System
- Models; Statistical
- Osmosis
- RNA; Messenger/metabolism
- Research Support; Non-U.S. Gov't
- Ribonucleases/metabolism
- Thyroid Neoplasms/*drug therapy/*metabolism/pathology
- Time Factors
- p38 Mitogen-Activated Protein Kinases/metabolism
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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