A histone deacetylase inhibitor YCW1 with antitumor and antimetastasis properties enhances cisplatin activity against non-small cell lung cancer in preclinical studies

Abstract Many histone deacetylase (HDAC) inhibitors show limited therapeutic effects for solid tumors. Here, we develop a novel HDAC inhibitor YCW1 and verify the combination effect of YCW1 and cisplatin in lung cancer pre-clinical models. YCW1 exerted cancer-specific cytotoxicity via mitochondria-m...

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Bibliographic Details
Published in:Cancer letters 2014-04, Vol.346 (1), p.84-93
Main Authors: Huang, Wei-Jan, Tang, Yen-An, Chen, Mei-Yu, Wang, Ying-Jan, Hu, Fu-Han, Wang, Tseng-Wei, Chao, Shi-Wei, Chiu, Hui-Wen, Yeh, Ya-Ling, Chang, Hsin-Yi, Juan, Hsueh-Fen, Lin, Pinpin, Wang, Yi-Ching
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Apoptosis
Autophagy
Azides - administration & dosage
Cancer therapies
Carcinoma, Non-Small-Cell Lung - drug therapy
Cisplatin
Cisplatin - administration & dosage
Deoxyribonucleic acid
DNA
DNA repair
Drug Synergism
Hematology, Oncology and Palliative Medicine
Histone deacetylase inhibitor
Histone Deacetylase Inhibitors - administration & dosage
Humans
Hydroxamic Acids - administration & dosage
Laboratory animals
Lung cancer
Lung Neoplasms - drug therapy
Male
Metastasis
Mice, Inbred BALB C
Non-small cell lung cancer
Reverse Transcriptase Polymerase Chain Reaction
Studies
Tumors
Xenograft Model Antitumor Assays
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Summary:Abstract Many histone deacetylase (HDAC) inhibitors show limited therapeutic effects for solid tumors. Here, we develop a novel HDAC inhibitor YCW1 and verify the combination effect of YCW1 and cisplatin in lung cancer pre-clinical models. YCW1 exerted cancer-specific cytotoxicity via mitochondria-mediated apoptosis. YCW1 and cisplatin showed synergistic anti-tumor effects through impairment of DNA damage repair. YCW1 inhibited tumor growth in lung orthotopic and subcutaneously implanted xenograft models. YCW1 significantly suppressed lung metastases via inhibition of focal adhesion complex. Our findings suggested that YCW1 is a potential HDAC inhibitor for lung cancer treatment as single and in combination regimens with cisplatin.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2013.12.016