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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MDPI AG
2023-02-01
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| author | Kishor Pant Seth Richard Estanislao Peixoto Jun Yin Davis M. Seelig Pietro Carotenuto Massimiliano Salati Brunella Franco Lewis R. Roberts Sergio A. Gradilone |
| author_facet | Kishor Pant Seth Richard Estanislao Peixoto Jun Yin Davis M. Seelig Pietro Carotenuto Massimiliano Salati Brunella Franco Lewis R. Roberts Sergio A. Gradilone |
| author_sort | Kishor Pant |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T07:28:27Z |
| format | Article |
| id | doaj.art-30ad4730341c47b49dd553c4ebcde208 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T07:28:27Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-30ad4730341c47b49dd553c4ebcde2082023-11-17T07:27:59ZengMDPI AGCells2073-44092023-02-0112577510.3390/cells12050775The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells GrowthKishor Pant0Seth Richard1Estanislao Peixoto2Jun Yin3Davis M. Seelig4Pietro Carotenuto5Massimiliano Salati6Brunella Franco7Lewis R. Roberts8Sergio A. Gradilone9The Hormel Institute, University of Minnesota, Austin, MN 55912, USAThe Hormel Institute, University of Minnesota, Austin, MN 55912, USAThe Hormel Institute, University of Minnesota, Austin, MN 55912, USADivision of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN 55905, USAComparative Pathology Shared Resource, Masonic Cancer Center, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USATelethon Institute of Genetics and Medicine (TIGEM), 80078 Pozzuoli, ItalyMedical Oncology Unit, University Hospital of Modena, 41125 Modena, ItalyMedical Genetics, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, ItalyDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USAThe Hormel Institute, University of Minnesota, Austin, MN 55912, USAIt 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.https://www.mdpi.com/2073-4409/12/5/775NAMPTNADFK866Cholangiocarcinomacisplatin |
| spellingShingle | Kishor Pant Seth Richard Estanislao Peixoto Jun Yin Davis M. Seelig Pietro Carotenuto Massimiliano Salati Brunella Franco Lewis R. Roberts Sergio A. Gradilone The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth Cells NAMPT NAD FK866 Cholangiocarcinoma cisplatin |
| 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 | NAMPT NAD FK866 Cholangiocarcinoma cisplatin |
| url | https://www.mdpi.com/2073-4409/12/5/775 |
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