2009
DOI: 10.1038/onc.2009.306
|View full text |Cite
|
Sign up to set email alerts
|

Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation

Abstract: Anaplastic thyroid carcinoma (ATC) is considered one of the most aggressive malignancies, having a poor prognosis and being refractory to conventional chemotherapy and radiotherapy. Alteration in histone deacetylase (HDAC) activity has been reported in cancer, thus encouraging the development of HDAC inhibitors, whose antitumor action has been shown in both solid and hematological malignancies. However, the molecular basis for their tumor selectivity is unknown. To find an innovative therapy for the treatment … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

1
44
1

Year Published

2010
2010
2017
2017

Publication Types

Select...
6
4

Relationship

0
10

Authors

Journals

citations
Cited by 65 publications
(46 citation statements)
references
References 49 publications
(57 reference statements)
1
44
1
Order By: Relevance
“…Indeed, cancer studies show that the mode of action of HDACi on selected genes is complex and dissociation of RNA and protein levels -eg, by inhibition of proteasomal degradation -has been repeatedly described. 51,52 In vivo, SMN levels in the spinal cord and brain of late-stage animals was higher than in untreated animals, but levels were still much lower than in the respective control littermates. In QF muscle levels of SMN in both treated and untreated SMA animals were even below detection by western blot analysis.…”
Section: Discussionmentioning
confidence: 96%
“…Indeed, cancer studies show that the mode of action of HDACi on selected genes is complex and dissociation of RNA and protein levels -eg, by inhibition of proteasomal degradation -has been repeatedly described. 51,52 In vivo, SMN levels in the spinal cord and brain of late-stage animals was higher than in untreated animals, but levels were still much lower than in the respective control littermates. In QF muscle levels of SMN in both treated and untreated SMA animals were even below detection by western blot analysis.…”
Section: Discussionmentioning
confidence: 96%
“…Thus, combining bortezomib with agents that additionally affect metabolism, sensitivity, and redifferentiation of ATC cells could improve the clinical outcome. For instance, in thyroid carcinoma cells, the histone deacetylase inhibitor MS-275 was shown to enhance the functional activity of NIS (25), and the combination of histone acetylase inhibitors and proteasome inhibitors synergistically enhanced TRAIL-mediated apoptosis (33). Thus, bortezomib may be considered a promising therapeutic agent for the treatment of anaplastic thyroid carcinoma in the setting of a combination therapy, but further investigation is clearly warranted to improve clinical outcome.…”
Section: Resultsmentioning
confidence: 99%
“…Therefore HDAC can be considered as potential therapeutic targets of human malignancies. Interestingly, the reduction of TRAIL protein degradation has been recently observed in thyroid cancer cells and proposed as a novel action of HDAC inhibitors (Borbone et al, 2010). It is worth outlining that HDAC inhibitors exert anti-tumour effects at doses that are well tolerated by the patients.…”
Section: Proteasome and Histone Deacetylase Inhibitorsmentioning
confidence: 97%