Inhibition of nicotinamide phosphoribosyltransferase and depletion of nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of oral squamous cell carcinoma

Journal Article · Fri Sep 15 04:00:00 EDT 2017 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2017.05.008· OSTI ID:22722920

Wang, Xin Yue ^[1]; Wang, Jin Zhi ^[2]; Gao, Lu ^[3]; Zhang, Fu Yin ^[2]; Wang, Qi ^[1]; Xiang, Bin ^[1]

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1. Laboratory of Oral and Maxillofacial Disease, Second Hospital of Dalian Medical University, Dalian, Liaoning 116023 (China)
2. Department of Oral and Maxillofacial Surgery, Second Hospital of Dalian Medical University, Dalian, Liaoning 116023 (China)
3. Department of Oral Anatomy, School of Stomatology, Dalian Medical University, Dalian, Liaoning 116044 (China)

Emerging evidence suggests that increased nicotinamide phosphoribosyltransferase (NAMPT) expression is associated with the development and prognosis of many cancers, but it remains unknown regarding its role in oral squamous cell carcinoma (OSCC). In the present study, the results from tissue microarray showed that NAMPT was overexpressed in OSCC patients and its expression level was directly correlated with differential grades of cancer. Interestingly, treatment of OSCC cells with chemotherapy agent arsenic trioxide (ATO) decreased the levels of NAMPT protein and increased cellular death in an ATO dose- and time-dependent manner. Most importantly, combination of low concentration ATO with FK866 (a NAMPT inhibitor) exerted enhanced inhibitive effect on NAMPT protein and mRNA expressions, leading to synergistic cytotoxicity on cancer cells through increasing cell apoptosis and depleting intracellular nicotinamide adenine dinucleotide levels. These findings demonstrate the crucial role of NAMPT in the prognosis of OSCC and reveal inhibition of NAMPT as a novel mechanism of ATO in suppressing cancer cell growth. Our results suggest that ATO can significantly enhance therapeutic efficacy of NAMPT inhibitor, and combined treatment may be a novel and effective therapeutic strategy for OSCC patients. - Highlights: • Level of overexpressed NAMPT is associated with differential grade of OSCC patients. • Arsenic trioxide (ATO) exerts anti-cancer effects through NAMPT inhibition. • ATO enhances tumor cell killing efficacy of NAMPT inhibitor through depleting NAD. • Combined ATO/NAMPT inhibitor may be a novel therapy for advanced OSCC patients.

• OSTI ID: 22722920
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 331; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENINES
ARSENIC
CARCINOMAS
CELL KILLING
INHIBITION
NAD
NICOTINAMIDE
PATIENTS
PLANT GROWTH
TIME DEPENDENCE
TUMOR CELLS