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

• Published in: Cancer letters Vol. 346; no. 1; pp. 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: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.04.2014; Elsevier Limited
• 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; Taiwan; Histone deacetylase inhibitor; Metastasis; Cisplatin; Non-small cell lung cancer; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2013.12.016

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.