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01-12-2013 | Translational Research and Biomarkers

Valproic Acid Sensitizes TRAIL-Resistant Anaplastic Thyroid Carcinoma Cells to Apoptotic Cell Death

Authors: Hyun-Young Cha, Bok-Soon Lee, PhD, Sam Kang, Yoo Seob Shin, MD, Jae Won Chang, MD, Eun-Sil Sung, PhD, Yong-Sung Kim, PhD, Jae Won Choi, Jang Hee Kim, MD, Chul-Ho Kim, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2013

Abstract

Background

Anaplastic thyroid carcinoma (ATC) is an aggressive human tumor associated with a median survival of 2–6 months. TRAIL, as a ligand of death receptors, is known to induce apoptotic cell death in several cancer cells. However, TRAIL treatment alone is not effective against TRAIL-resistant cancer cells. This study was designed to investigate whether valproic acid (VPA) enhances apoptotic cell death of TRAIL-resistant ATC cells and to identify the mechanism of cell death of ATC cells by combination treatment with VPA and TRAIL.

Methods

To evaluate the cytotoxic effect of TRAIL and/or VPA on ATC cells, we used the MTT assay. The effects of VPA and TRAIL on apoptosis were assessed using FACS analysis (Annexin-V/PI stain) and Western blotting.

Results

The combination of VPA with TRAIL significantly induced apoptotic cell death compared with 8505C and ARO cells treated with TRAIL alone. The protein levels of cleaved caspase-8, -3, and PARP were increased in VPA and TRAIL co-treated ARO cells. The combination induced the activation of JNK and the phosphorylation of FADD and c-Jun but not p38. However, pretreatment with caspase inhibitors reduced the expression of cleaved caspase-8, -3, and PARP in co-treated ARO cells. SP600125 remarkably reduced the expression of cleaved caspase-8, -3, and PARP and the phosphorylation of FADD and c-Jun, as well as apoptotic cell death.

Conclusions

VPA sensitized TRAIL-resistant ATC cells to apoptotic cell death through involvement of the JNK pathway. Thus, the combination of VPA and TRAIL may be a promising therapy for ATC.

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Title: Valproic Acid Sensitizes TRAIL-Resistant Anaplastic Thyroid Carcinoma Cells to Apoptotic Cell Death
Authors: Hyun-Young Cha
Bok-Soon Lee, PhD
Sam Kang
Yoo Seob Shin, MD
Jae Won Chang, MD
Eun-Sil Sung, PhD
Yong-Sung Kim, PhD
Jae Won Choi
Jang Hee Kim, MD
Chul-Ho Kim, MD, PhD
Publication date: 01-12-2013
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-013-3232-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Valproic Acid Sensitizes TRAIL-Resistant Anaplastic Thyroid Carcinoma Cells to Apoptotic Cell Death

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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