Startseite Naturwissenschaften Effect of non-competitive inhibitors of aminopeptidase N on viability of human and murine tumor cells
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Effect of non-competitive inhibitors of aminopeptidase N on viability of human and murine tumor cells

  • Isel Pascual Alonso EMAIL logo , Gabriela García , Lisset Díaz , Yarini Arrebola , Laura Rivera Méndez , Fabiola Almeida García , Mae Chappé Pacheco , Belinda Sánchez und Jean-Louis Charli
Veröffentlicht/Copyright: 22. September 2021
Pure and Applied Chemistry
Aus der Zeitschrift Pure and Applied Chemistry Band 93 Heft 10

Abstract

Cancer is the second leading cause of death worldwide. Peptidases participate in tumor development and growth. Mammalian neutral aminopeptidase (APN, EC 3.4.11.2, M1 family) catalyzes the cleavage of neutral and basic amino acids from the N-terminus of substrates. APN expression is dysregulated in several types of cancer, being a target for the development of new anticancer agents. Recently, we identified three new non-competitive inhibitors of soluble porcine APN (pAPN) by virtual screening (BTB11079, JFD00064, BTB07018, from Maybridge). In the present contribution we assayed their effect on the activity of APN in a microsomal preparation of porcine kidney cortex, a model of the physicochemical environment of the enzyme. These classical inhibitors had an IC50 value of 3–5 µM. Additionally, using a kinetic approach and a specific substrate, we quantified APN activity on the cell surface of human and murine lung, colon, prostate, and skin tumor cells. APN inhibitors reduced tumor cells viability, more efficiently in the higher APN activity tumor cell lines, but not in non-tumoral cells. BTB11079, JFD00064, BTB07018 effects on cell viability were stronger than that of bestatin, a positive control. Thus, these non-competitive APN inhibitors may be useful tools for cancer treatment.

Keywords: Cell viability; inhibitors; neutral aminopeptidase; tumor cell; Virtual Conference on Chemistry and its Applications
Corresponding author: Isel Pascual Alonso, Center for Protein Studies, Faculty of Biology, University of Havana, Cuba. 25 # 455, between J and I, Plaza de la Revolución, Havana, CP 10 400, Cuba, Phone: +53 (7) 8324830, Fax: +53 (7) 8321321, e-mail:

Article note: A collection of invited papers based on presentations at the Virtual Conference on Chemistry and its Applications (VCCA-2020) held on-line, 1–31 August 2020.

Funding source: Universitary Laboratory in Nanotechnology and Cancer (NaNoCancer)

Funding source: Oficina de Gestión de Fondos y Proyectos Internacionales del Ministerio de Ciencia, Tecnología y Medio Ambiente de la República de Cuba

Award Identifier / Grant number: PN223LH010-010

Acknowledgments

We thank technician D. Diaz for her support in microsomal preparation.

  1. Research funding: This work was supported by the Universitary Laboratory in Nanotechnology and Cancer (NaNoCancer) project: “New inhibitors of aminopeptidases with potential applications in cancer” (2016-2020) and by “Oficina de Gestión de Fondos y Proyectos Internacionales del Ministerio de Ciencia, Tecnología y Medio Ambiente de la República de Cuba”, code PN223LH010-010.

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Published Online: 2021-09-22
Published in Print: 2021-10-26

© 2021 IUPAC & De Gruyter. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. For more information, please visit: http://creativecommons.org/licenses/by-nc-nd/4.0/

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Preface
  4. Celebrating a centenary of macromolecules
  5. Invited papers
  6. Hermann Staudinger – Organic chemist and pioneer of macromolecules
  7. On cellulose spatial organization and interactions as unraveled by diffraction and spectroscopic methods throughout the 20th century
  8. Dielectric properties of processed cheese
  9. Drawing inspiration from nature to develop anti-fouling coatings: the development of biomimetic polymer surfaces and their effect on bacterial fouling
  10. Mitigating the charge trapping effects of D-sorbitol/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) polymer blend contacts to crystalline silicon
  11. Influence of thermal treatment on the properties and intermolecular interactions of epoxidized natural rubber-salt systems
  12. Leveraging diversity and inclusion in the polymer sciences: the key to meeting the rapidly changing needs of our world
  13. Preface
  14. The virtual conference on chemistry and its applications, VCCA-2020, 1–31 August 2020
  15. Conference papers
  16. Effect of non-competitive inhibitors of aminopeptidase N on viability of human and murine tumor cells
  17. Evaluation of the catalytic activity of graphene oxide and zinc oxide nanoparticles on the electrochemical sensing of T1R2-Rebaudioside A complex supported by in silico methods
  18. Maximizing student learning through the use of demonstrations
  19. Molecular spaces and the dimension paradox
  20. Reaction of •OH with CHCl=CH-CHF2 and its atmospheric implication for future environmental-friendly refrigerant
  21. In silico study of the synergistic anti-tumor effect of hybrid topoisomerase-HDAC inhibitors
  22. Structural and electronic properties of Cu4O3 (paramelaconite): the role of native impurities
https://doi.org/10.1515/pac-2020-1010
Schlagwörter für diesen Artikel
Cell viability; inhibitors; neutral aminopeptidase; tumor cell; Virtual Conference on Chemistry and its Applications

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Preface
  4. Celebrating a centenary of macromolecules
  5. Invited papers
  6. Hermann Staudinger – Organic chemist and pioneer of macromolecules
  7. On cellulose spatial organization and interactions as unraveled by diffraction and spectroscopic methods throughout the 20th century
  8. Dielectric properties of processed cheese
  9. Drawing inspiration from nature to develop anti-fouling coatings: the development of biomimetic polymer surfaces and their effect on bacterial fouling
  10. Mitigating the charge trapping effects of D-sorbitol/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) polymer blend contacts to crystalline silicon
  11. Influence of thermal treatment on the properties and intermolecular interactions of epoxidized natural rubber-salt systems
  12. Leveraging diversity and inclusion in the polymer sciences: the key to meeting the rapidly changing needs of our world
  13. Preface
  14. The virtual conference on chemistry and its applications, VCCA-2020, 1–31 August 2020
  15. Conference papers
  16. Effect of non-competitive inhibitors of aminopeptidase N on viability of human and murine tumor cells
  17. Evaluation of the catalytic activity of graphene oxide and zinc oxide nanoparticles on the electrochemical sensing of T1R2-Rebaudioside A complex supported by in silico methods
  18. Maximizing student learning through the use of demonstrations
  19. Molecular spaces and the dimension paradox
  20. Reaction of •OH with CHCl=CH-CHF2 and its atmospheric implication for future environmental-friendly refrigerant
  21. In silico study of the synergistic anti-tumor effect of hybrid topoisomerase-HDAC inhibitors
  22. Structural and electronic properties of Cu4O3 (paramelaconite): the role of native impurities
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