Open AccessAlteration of cancer stem cell‐like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck
Author(s) -
Chikamatsu Kazuaki,
Ishii Hiroki,
Murata Takaaki,
Sakakura Koichi,
Shino Masato,
Toyoda Minoru,
Takahashi Katsumasa,
Masuyama Keisuke
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12271
Subject(s) - histone deacetylase , phenotype , cancer research , head and neck , histone deacetylase inhibitor , basal cell , stem cell , head and neck squamous cell carcinoma , cell , head and neck cancer , cancer , biology , squamous cell cancer , histone , cancer stem cell , medicine , pathology , microbiology and biotechnology , genetics , gene , surgery
Recent progression in the understanding of stem cell biology has greatly facilitated the identification and characterization of cancer stem cells ( CSC s). Moreover, evidence has accumulated indicating that conventional cancer treatments are potentially ineffective against CSCs . Histone deacetylase inhibitors ( HDAC i) have multiple biologic effects consequent to alterations in the patterns of acetylation of histones and are a promising new group of anticancer agents. In this study, we investigated the effects of two HDAC i, suberoylanilide hydroxamic acid ( SAHA ) and trichostatin A ( TSA ), on two CD 44+ cancer stem‐like cell lines from squamous cell carcinoma of the head and neck ( SCCHN ) cultured in serum‐free medium containing epidermal growth factor and basic fibroblast growth factor. Histone deacetylase inhibitors inhibited the growth of SCCHN cell lines in a dose‐dependent manner as measured by MTS assays. Moreover, HDAC i induced cell cycle arrest and apoptosis in these SCCHN cell lines. Interestingly, the expression of cancer stem cell markers, CD 44 and ABCG 2, on SCCHN cell lines was decreased by HDAC i treatment. In addition, HDAC i decreased mRNA expression levels of stemness‐related genes and suppressed the epithelial‐mesencymal transition phenotype of CSC s. As expected, the combination of HDACi and chemotherapeutic agents, including cisplatin and docetaxel, had a synergistic effect on SCCHN cell lines. Taken together, our data indicate that HDAC i not only inhibit the growth of SCCHN cell lines by inducing apoptosis and cell cycle arrest, but also alter the cancer stem cell phenotype in SCCHN , raising the possibility that HDAC i may have therapeutic potential for cancer stem cells of SCCHN .