Author/Authors :
Huang، نويسنده , , Wei-Jan and Tang، نويسنده , , Yen-An and Chen، نويسنده , , Mei-Yu and Wang، نويسنده , , Ying-Jan and Hu، نويسنده , , Fu-Han and Wang، نويسنده , , Tseng-Wei and Chao، نويسنده , , Shi-Wei and Chiu، نويسنده , , Hui-Wen and Yeh، نويسنده , , Ya-Ling and Chang، نويسنده , , Hsin-Yi and Juan، نويسنده , , Hsueh-Fen and Lin، نويسنده , , Pinpin and Wang، نويسنده , , Yi-Ching، نويسنده ,
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.
Keywords :
Histone deacetylase inhibitor , Cisplatin , apoptosis , Non-small cell lung cancer , metastasis