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.

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.

• Authors: Turki Y Alhazzazi, Pachiyappan Kamarajan, Yanli Xu, Teng Ai, Liqiang Chen, Eric Verdin, Yvonne L Kapila
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 1 Pg. 49-60 (Jan 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26722027 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Heterocyclic Compounds, 4 or More Rings
• Histone Deacetylase Inhibitors
• Indoles
• LC-0296
• Reactive Oxygen Species
• SIRT3 protein, human
• Sirtuin 3
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (drug therapy, enzymology, pathology, radiotherapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemoradiotherapy
• Cisplatin (pharmacology)
• Dose-Response Relationship, Drug
• Head and Neck Neoplasms (drug therapy, enzymology, pathology, radiotherapy)
• Heterocyclic Compounds, 4 or More Rings (pharmacology)
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• Indoles (pharmacology)
• Keratinocytes (drug effects, metabolism, pathology)
• Laryngeal Neoplasms (drug therapy, enzymology, pathology, radiotherapy)
• Mouth Neoplasms (drug therapy, enzymology, pathology, radiotherapy)
• Radiation Tolerance
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Sirtuin 3 (antagonists & inhibitors, metabolism)
• Squamous Cell Carcinoma of Head and Neck