Next Article in Journal
Cecropin A Modulates Tight Junction-Related Protein Expression and Enhances the Barrier Function of Porcine Intestinal Epithelial Cells by Suppressing the MEK/ERK Pathway
Next Article in Special Issue
Differences in Functional Expression of Connexin43 and NaV1.5 by Pan- and Class-Selective Histone Deacetylase Inhibition in Heart
Previous Article in Journal
ABA Receptor Subfamily III Enhances Abscisic Acid Sensitivity and Improves the Drought Tolerance of Arabidopsis
Open AccessReview

Therapeutic Opportunities of Targeting Histone Deacetylase Isoforms to Eradicate Cancer Stem Cells

1
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
2
School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan
3
Department of Cosmeceutics and Graduate Institute of Cosmeceutics, China Medical University, Taichung 40402, Taiwan
4
Drug Development Center, China Medical University, Taichung 40402, Taiwan
5
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(7), 1939; https://doi.org/10.3390/ijms19071939
Received: 1 June 2018 / Revised: 22 June 2018 / Accepted: 29 June 2018 / Published: 2 July 2018
(This article belongs to the Special Issue Histone Deacetylase Inhibitors in Health and Disease)
Cancer stem cells (CSCs), or tumor-initiating cells, are a small subset of cancer cells with the capacity for self-renewal and differentiation, which have been shown to drive tumor initiation, progression, and metastasis in many types of cancer. Moreover, therapeutic regimens, such as cisplatin and radiation were reported to induce the enrichment of CSCs, thereby conferring chemoresistance on cancer cells. Therefore, therapeutic targeting of CSCs represents a clinical challenge that needs to be addressed to improve patient outcome. In this context, the effectiveness of pan or class-I histone deacetylase (HDAC) inhibitors in suppressing the CSC population is especially noteworthy in light of the new paradigm of combination therapy. Evidence suggests that this anti-CSC activity is associated with the ability of HDAC inhibitors to target multiple signaling pathways at different molecular levels. Beyond chromatin remodeling via histone acetylation, HDAC inhibitors can also block key signaling pathways pertinent to CSC maintenance. Especially noteworthy is the ability of different HDAC isoforms to regulate the protein stability and/or activity of a series of epithelial-mesenchymal transition (EMT)-inducing transcription factors, including HIF-1α, Stat3, Notch1, β-catenin, NF-κB, and c-Jun, each of which plays a critical role in regulating CSCs. From the translational perspective, these mechanistic links constitute a rationale to develop isoform-selective HDAC inhibitors as anti-CSC agents. Thus, this review aims to provide an overview on the roles of HDAC isoforms in maintaining CSC homeostasis via distinct signaling pathways independent of histone acetylation. View Full-Text
Keywords: histone deacetylases; cancer stem cells; non-histone targets; acetylation status; chaperon proteins; transcription factors histone deacetylases; cancer stem cells; non-histone targets; acetylation status; chaperon proteins; transcription factors
Show Figures

Figure 1

MDPI and ACS Style

Lin, P.-C.; Hsieh, H.-Y.; Chu, P.-C.; Chen, C.S. Therapeutic Opportunities of Targeting Histone Deacetylase Isoforms to Eradicate Cancer Stem Cells. Int. J. Mol. Sci. 2018, 19, 1939. https://doi.org/10.3390/ijms19071939

AMA Style

Lin P-C, Hsieh H-Y, Chu P-C, Chen CS. Therapeutic Opportunities of Targeting Histone Deacetylase Isoforms to Eradicate Cancer Stem Cells. International Journal of Molecular Sciences. 2018; 19(7):1939. https://doi.org/10.3390/ijms19071939

Chicago/Turabian Style

Lin, Peng-Chan; Hsieh, Hao-Yu; Chu, Po-Chen; Chen, Ching S. 2018. "Therapeutic Opportunities of Targeting Histone Deacetylase Isoforms to Eradicate Cancer Stem Cells" Int. J. Mol. Sci. 19, no. 7: 1939. https://doi.org/10.3390/ijms19071939

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop