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

作者：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

来源：Cancer Letters, 2014, 346(1): 84-93.

DOI：10.1016/j.canlet.2013.12.016

• Histone deacetylase inhibitor
• Cisplatin
• Apoptosis
• Metastasis
• Non-small cell lung cancer

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.

• 出版日期2014-4-28