Turki Y Alhazzazi1, Pachiyappan Kamarajan2, Yanli Xu3, Teng Ai3, Liqiang Chen3, Eric Verdin4, Yvonne L Kapila5. 1. 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. 2. Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A. 3. Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN, U.S.A. 4. Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, U.S.A. 5. Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A. ykapila@umich.edu.
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. MATERIALS AND 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. CONCLUSION: 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. Copyright
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. MATERIALS AND 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. CONCLUSION: 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. Copyright
Authors: Heikki S Salo; Tuomo Laitinen; Antti Poso; Elina Jarho; Maija Lahtela-Kakkonen Journal: Bioorg Med Chem Lett Date: 2013-03-16 Impact factor: 2.823
Authors: Sumit S Mahajan; Michele Scian; Smitha Sripathy; Jeff Posakony; Uyen Lao; Taylor K Loe; Vid Leko; Angel Thalhofer; Aaron D Schuler; Antonio Bedalov; Julian A Simon Journal: J Med Chem Date: 2014-04-15 Impact factor: 7.446
Authors: Karsten Krug; Eric J Jaehnig; Shankha Satpathy; Lili Blumenberg; Alla Karpova; Meenakshi Anurag; George Miles; Philipp Mertins; Yifat Geffen; Lauren C Tang; David I Heiman; Song Cao; Yosef E Maruvka; Jonathan T Lei; Chen Huang; Ramani B Kothadia; Antonio Colaprico; Chet Birger; Jarey Wang; Yongchao Dou; Bo Wen; Zhiao Shi; Yuxing Liao; Maciej Wiznerowicz; Matthew A Wyczalkowski; Xi Steven Chen; Jacob J Kennedy; Amanda G Paulovich; Mathangi Thiagarajan; Christopher R Kinsinger; Tara Hiltke; Emily S Boja; Mehdi Mesri; Ana I Robles; Henry Rodriguez; Thomas F Westbrook; Li Ding; Gad Getz; Karl R Clauser; David Fenyö; Kelly V Ruggles; Bing Zhang; D R Mani; Steven A Carr; Matthew J Ellis; Michael A Gillette Journal: Cell Date: 2020-11-18 Impact factor: 41.582
Authors: Chandra K Singh; Gagan Chhabra; Mary Ann Ndiaye; Liz Mariely Garcia-Peterson; Nicholas J Mack; Nihal Ahmad Journal: Antioxid Redox Signal Date: 2017-10-20 Impact factor: 8.401