title: Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells.
abstract: Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents. The subpopulation of highly invasive NSCLC cells showed epigenetic signatures of epithelial-mesenchymal transition, cancer cell stemness, increased DNA damage repair and cell survival signaling. We also investigated the epigenetic therapy potential of suberoylanilide hydroxamic acid (SAHA) on invasive cancer cells, and found that SAHA suppresses cancer cell invasiveness and sensitizes cancer cells to treatments of IR and chemotherapeutic agents. Our results provide guidelines for identification of metastatic predictors and for clinical management of NSCLC. This study also suggests a beneficial clinical potential of SAHA as a chemotherapeutic agent for NSCLC patients.
authors.affiliation: Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Shirong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Affiliated Hangzhou First People's Hospital of Zhejiang Chinese Medical University, Hangzhou, China.|Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Wu
authors.affiliation: Cancer Research institute, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Cancer Genetics and Epigenetics, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Haixiu
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Lucheng
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Cancer Genetics and Epigenetics, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Binghui
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008564:Membrane Potentials; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat
keywords: epigenetic therapy; epigenetics; invasion; non-small cell lung cancer; suberoylanilide hydroxamic acid