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The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth

It is well established that Cholangiocarcioma (CCA) drug resistance plays a crucial role in the spread and survival of cancer cells. The major enzyme in the nicotinamide-adenine dinucleotide (NAD+)-mediated pathways, nicotinamide phosphoribosyltransferase (NAMPT), is essential for cancer cell surviv...

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Autores principales: Pant, Kishor, Richard, Seth, Peixoto, Estanislao, Yin, Jun, Seelig, Davis M., Carotenuto, Pietro, Salati, Massimiliano, Franco, Brunella, Roberts, Lewis R., Gradilone, Sergio A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10001024/
https://www.ncbi.nlm.nih.gov/pubmed/36899911
http://dx.doi.org/10.3390/cells12050775
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author Pant, Kishor
Richard, Seth
Peixoto, Estanislao
Yin, Jun
Seelig, Davis M.
Carotenuto, Pietro
Salati, Massimiliano
Franco, Brunella
Roberts, Lewis R.
Gradilone, Sergio A.
author_facet Pant, Kishor
Richard, Seth
Peixoto, Estanislao
Yin, Jun
Seelig, Davis M.
Carotenuto, Pietro
Salati, Massimiliano
Franco, Brunella
Roberts, Lewis R.
Gradilone, Sergio A.
author_sort Pant, Kishor
collection PubMed
description It is well established that Cholangiocarcioma (CCA) drug resistance plays a crucial role in the spread and survival of cancer cells. The major enzyme in the nicotinamide-adenine dinucleotide (NAD+)-mediated pathways, nicotinamide phosphoribosyltransferase (NAMPT), is essential for cancer cell survival and metastasis. Previous research has shown that the targeted NAMPT inhibitor FK866 reduces cancer cell viability and triggers cancer cell death; however, whether FK866 affects CCA cell survival has not been addressed before. We show herein that NAMPT is expressed in CCA cells, and FK866 suppresses the capacity of CCA cells to grow in a dose-dependent manner. Furthermore, by preventing NAMPT activity, FK866 significantly reduced the amount of NAD+ and adenosine 5′-triphosphate (ATP) in HuCCT1, KMCH, and EGI cells. The present study’s findings further show that FK866 causes changes in mitochondrial metabolism in CCA cells. Additionally, FK866 enhances the anticancer effects of cisplatin in vitro. Taken together, the results of the current study suggest that the NAMPT/NAD+ pathway may be a possible therapeutic target for CCA, and FK866 may be a useful medication targeting CCA in combination with cisplatin.
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spelling pubmed-100010242023-03-11 The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth Pant, Kishor Richard, Seth Peixoto, Estanislao Yin, Jun Seelig, Davis M. Carotenuto, Pietro Salati, Massimiliano Franco, Brunella Roberts, Lewis R. Gradilone, Sergio A. Cells Article It is well established that Cholangiocarcioma (CCA) drug resistance plays a crucial role in the spread and survival of cancer cells. The major enzyme in the nicotinamide-adenine dinucleotide (NAD+)-mediated pathways, nicotinamide phosphoribosyltransferase (NAMPT), is essential for cancer cell survival and metastasis. Previous research has shown that the targeted NAMPT inhibitor FK866 reduces cancer cell viability and triggers cancer cell death; however, whether FK866 affects CCA cell survival has not been addressed before. We show herein that NAMPT is expressed in CCA cells, and FK866 suppresses the capacity of CCA cells to grow in a dose-dependent manner. Furthermore, by preventing NAMPT activity, FK866 significantly reduced the amount of NAD+ and adenosine 5′-triphosphate (ATP) in HuCCT1, KMCH, and EGI cells. The present study’s findings further show that FK866 causes changes in mitochondrial metabolism in CCA cells. Additionally, FK866 enhances the anticancer effects of cisplatin in vitro. Taken together, the results of the current study suggest that the NAMPT/NAD+ pathway may be a possible therapeutic target for CCA, and FK866 may be a useful medication targeting CCA in combination with cisplatin. MDPI 2023-02-28 /pmc/articles/PMC10001024/ /pubmed/36899911 http://dx.doi.org/10.3390/cells12050775 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pant, Kishor
Richard, Seth
Peixoto, Estanislao
Yin, Jun
Seelig, Davis M.
Carotenuto, Pietro
Salati, Massimiliano
Franco, Brunella
Roberts, Lewis R.
Gradilone, Sergio A.
The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth
title The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth
title_full The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth
title_fullStr The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth
title_full_unstemmed The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth
title_short The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth
title_sort nampt inhibitor fk866 in combination with cisplatin reduces cholangiocarcinoma cells growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10001024/
https://www.ncbi.nlm.nih.gov/pubmed/36899911
http://dx.doi.org/10.3390/cells12050775
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