Histone deacetylase 7 silencing induces apoptosis and autophagy in salivary mucoepidermoid carcinoma cells.
BACKGROUND
The overexpression of histone deacetylases (HDACs) has been observed in many cancers, and inhibition of specific HDACs has emerged as a new target for cancer therapy. We found that HDAC7 expression was selectively reduced by HDAC inhibitor apicidin in salivary mucoepidermoid carcinoma (MEC) cells. Here, we show that HDAC7 suppression has a potent antitumor effect in MEC cells.


METHODS
Histone deacetylases7 was knocked down using HDAC7 siRNAs, and cell proliferation was quantified. Cell cycle progression, apoptosis, and autophagy were measured by flow cytometry and immunoblotting.


RESULTS
Histone deacetylases 7 siRNAs inhibited cell proliferation and c-Myc expression, increased p27 expression, and caused G2/M phase cell cycle arrest in both YD-15 and Mc3 cells. HDAC7 silencing increased the sub-G1 population, Annexin V positive apoptotic cells and cleaved caspase3 levels. HDAC7 silencing induced an increase in autophagic markers, number of acidic vesicular organelles, and LC3B II levels, and decrease in p62 levels. HDAC7 siRNAs reduced the activation of ERK. HDAC7 knockdown resulted in growth inhibition through G2/M phase cell cycle arrest and induced both apoptosis and autophagy in MEC cells.


CONCLUSIONS
This study indicates that inhibition of HDAC7 might become a novel and effective therapeutic approach for treating to MEC.
Division of Bio-industry, Major in Pharmaceutical Engineering, College of Medical and Life Sciences, Silla University, Busan, Korea.
Mee-Young
MY
Ahn
Department of Oral & Maxillofacial Pathology, Wonkwang Bone Regeneration Research Institute, College of Dentistry, Daejeon Dental Hospital, Wonkwang University, Daejeon, Korea.
Jung-Hoon
http://orcid.org/0000-0002-6331-2736
JH
Yoon
D017209:Apoptosis; D001343:Autophagy; D018277:Carcinoma, Mucoepidermoid / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D012468:Salivary Gland Neoplasms / Q000378:metabolism*
C543273:HDAC7 protein, human; D006655:Histone Deacetylases
G2/M phase arrest; apoptosis; autophagy; histone deacetylases 7; salivary mucoepidermoid carcinoma