title: A Novel Sirtuin-3 Inhibitor, LC-0296, Inhibits Cell Survival and Proliferation, and Promotes Apoptosis of Head and Neck Cancer Cells.
abstract: BACKGROUND
  The survival rate of patients with head and neck squamous cell carcinoma (HNSCC) stands at approximately 50% and this has not improved in decades. This study developed a novel sirtuin-3 (SIRT3) inhibitor (LC-0296) and examined its role in altering HNSCC tumorigenesis.
  
  
  METHODS
  The effect of the SIRT3 inhibitor, LC-0296, on cell survival, proliferation, and apoptosis, and reactive oxygen species levels in HNSCC cells were studied.
  
  
  RESULTS
  LC-0296 reduces cell proliferation and promotes apoptosis of HNSCC cells but not of normal human oral keratinocytes. This inhibitory effect is mediated, in part, via modulation of reactive oxygen species levels. Additionally, LC-0296 works synergistically to increase the sensitivity of HNSCC cells to radiation and cisplatin treatment.
  
  
  CONCLUSIONS
  Development of novel SIRT3 inhibitors, such as LC-0296, might enable the development of new targeted therapies to treat and improve the survival rate of patients with head and neck cancer.
authors.affiliation: Department of Oral Biology, King Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Turki Y
authors.initials: TY
authors.lastname: Alhazzazi
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Pachiyappan
authors.initials: P
authors.lastname: Kamarajan
authors.affiliation: Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN, U.S.A.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN, U.S.A.
authors.forename: Teng
authors.initials: T
authors.lastname: Ai
authors.affiliation: Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN, U.S.A.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, U.S.A.
authors.forename: Eric
authors.initials: E
authors.lastname: Verdin
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A. ykapila@umich.edu.
authors.forename: Yvonne L
authors.initials: YL
authors.lastname: Kapila
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056566:Sirtuin 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D056572:Histone Deacetylase Inhibitors; D007211:Indoles; C000607225:LC-0296; D017382:Reactive Oxygen Species; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D002945:Cisplatin
keywords: HNSCC; ROS; SIRT3; Sirtuins; oral cancer; sirtuin inhibitor; sirtuin-3