A histone deacetylase inhibitor YCW1 with antitumor and antimetastasis properties enhances cisplatin activity against non-small cell lung cancer in preclinical studies.
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.
['Huang|Wei-Jan|WJ|', 'Tang|Yen-An|YA|', 'Chen|Mei-Yu|MY|', 'Wang|Ying-Jan|YJ|', 'Hu|Fu-Han|FH|', 'Wang|Tseng-Wei|TW|', 'Chao|Shi-Wei|SW|', 'Chiu|Hui-Wen|HW|', 'Yeh|Ya-Ling|YL|', 'Chang|Hsin-Yi|HY|', 'Juan|Hsueh-Fen|HF|', 'Lin|Pinpin|P|', 'Wang|Yi-Ching|YC|']
D000818:Animals D000971:Antineoplastic Combined Chemotherapy Protocols D001386:Azides D002289:Carcinoma, Non-Small-Cell Lung D002945:Cisplatin D004357:Drug Synergism D056572:Histone Deacetylase Inhibitors D006801:Humans D006877:Hydroxamic Acids D008175:Lung Neoplasms D008297:Male D008807:Mice, Inbred BALB C D020133:Reverse Transcriptase Polymerase Chain Reaction D023041:Xenograft Model Antitumor Assays
Histone deacetylase inhibitor Cisplatin Non-small cell lung cancer Apoptosis Metastasis