title: 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-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.
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Huang
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Yen-An
authors.initials: YA
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Ying-Jan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Fu-Han
authors.initials: FH
authors.lastname: Hu
authors.affiliation: Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan, ROC.
authors.forename: Tseng-Wei
authors.initials: TW
authors.lastname: Wang
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Chao
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chiu
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Yeh
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
authors.affiliation: Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan, ROC. Electronic address: 950136@nhri.org.tw.
authors.forename: Pinpin
authors.initials: P
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC; Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: ycw5798@mail.ncku.edu.tw.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Wang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001386:Azides / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D004357:Drug Synergism; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: D001386:Azides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C561227:octanedioic acid (1-(3-azido-5-azidomethylbenzyl)-1H-pyrazol-4-yl)amide hydroxyamide; D002945:Cisplatin
keywords: Apoptosis; Cisplatin; Histone deacetylase inhibitor; Metastasis; Non-small cell lung cancer