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

Kishor Pant, Seth Richard, Estanislao Peixoto, Jun Yin, Davis M. Seelig, Pietro Carotenuto, Massimiliano Salati, Brunella Franco, Lewis R. Roberts, Sergio A. Gradilone

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number775
JournalCells
Volume12
Issue number5
DOIs
StatePublished - Mar 2023

Bibliographical note

Funding Information:
This work was supported by The Hormel Foundation. Part of the study was kindly supported by POR CAMPANIA FESR 2014/2020 grant (Project titles: “Dalla genomica alla terapia di tumori rari” and “Combattere la resistenza tumorale: piattaforma integrata multidisciplinare per un approccio tecnologico innovativo alle concoterapie; CUP B61G18000470007) by the Italian Association for Cancer Research (AIRC) (grant n. IG 17711/2015 to B.F.). P.C. is a current recipient of a Marie Skłodowska-Curie Career Re-Integration fellowship funded by AIRC and the European Union’s Horizon 2020 research and innovation program (Grant agreement No 800924).

Publisher Copyright:
© 2023 by the authors.

Keywords

  • Cholangiocarcinoma
  • FK866
  • NAD
  • NAMPT
  • cisplatin

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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