Open AccessInhibition of Nicotinamide Phosphoribosyltransferase Induces Apoptosis in Estrogen Receptor-Positive MCF-7 Breast Cancer Cells
Author(s) -
Mohammad Reza Alaee,
Shahnaz Khaghani,
Kiarash Behroozfar,
Zahra Hesari,
Seyedeh Sara Ghorbanhosseini,
Mitra Nourbakhsh
Publication year - 2017
Publication title -
journal of breast cancer/journal of breast cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 36
eISSN - 2092-9900
pISSN - 1738-6756
DOI - 10.4048/jbc.2017.20.1.20
Subject(s) - nicotinamide phosphoribosyltransferase , nad+ kinase , estrogen receptor , cancer research , nicotinamide adenine dinucleotide , nicotinamide , apoptosis , mcf 7 , propidium iodide , biology , cancer cell , microbiology and biotechnology , biochemistry , medicine , programmed cell death , cancer , breast cancer , enzyme , human breast
Tumor cells have increased turnover of nicotinamide adenine dinucleotide (NAD + ), the main coenzyme in processes including adenosine diphosphate-ribosylation, deacetylation, and calcium mobilization. NAD + is predominantly synthesized in human cells via the salvage pathway, with the first component being nicotinamide. Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in this pathway, and its chemical inhibition by FK866 has elicited antitumor effects in several preclinical models of solid and hematologic cancers. However, its efficacy in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2-positive breast cancer cells has not been previously investigated. In this study, we aimed to deplete the NAD + content of MCF-7 cells, a model cell line for ER-positive breast cancer, by inhibiting NAMPT in order to evaluate downstream effects on p53 and its acetylation, p21 and Bcl-2-associated X protein (BAX) expression, and finally, apoptosis in MCF-7 breast cancer cells.