Focal adhesion kinase inhibition decreases cell viability and induces apoptosis of JAK2 V617F positive cells

Authors

DOI:

https://doi.org/10.1590/

Keywords:

FAK;, Apoptosis;, Myeloproliferative Neoplasms

Abstract

Focal Adhesion Kinase (FAK) protein participates in proliferation, migration, cell survival, and apoptosis process. It has been described as overexpressed in several neoplasms being a promising target for therapy. BCR-ABL negative chronic Myeloproliferative Neoplasms (MPN) are clonal disorders characterized by the excess of proliferation and apoptosis resistance. The identification of the acquired JAK2 V617F mutation in MPN patients allowed a better understanding of pathogenesis. However, there is still no pharmacological treatment that leads all patients to molecular remission, justifying new studies. The present study aimed to evaluate FAK involvement in the viability and apoptosis of HEL and SET-2 cells, both JAK2 V617F positive cell lines. The FAK inhibitor PF 562,271 was used. Cell viability was determined using MTT assay and apoptosis verified by cleaved PARP, cleaved Caspase 3 and Annexin-V/PI staining detection. FAK inhibition significantly reduced HEL and SET-2 cells viability and induced apoptosis. Considering the role of JAK/STAT pathway in MPN, further investigation of FAK participation in the MPN cells proliferation and apoptosis resistance, as well as possible crosstalk between JAK and FAK and downstream pathways may contribute to the knowledge of MPN pathophysiology, the discovery of new molecular targets, and JAK inhibitors resistance mechanisms.

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Author Biographies

  • Ana Carolina Menezes Mendonça Valente, Universidade Federal de Juiz de Fora, MG, Brazil
    Performed experiments Analyzed data Wrote the manuscript Critically revised the manuscript.
  • Gustavo Henrique Lima de Farias, Universidade Federal de Juiz de Fora, MG, Brazil
    Performed experiments Critically revised the manuscript.
  • Ana Cristina Ribeiro Bernardo, Universidade Federal de Juiz de Fora, MG, Brazil
    Performed experiments Critically revised the manuscript.
  • Caio Cesar de Souza Alves, Universidade Federal dos Vales do Jequitinhonha e Mucuri. Faculdade de Medicina do Mucuri, Campus Mucuri, Teófilo Otoni, MG, Brazil
    Performed flow cytometry experiments Critically revised the manuscript.
  • Michelle Bueno de Moura Pereira, Universidade Federal de Juiz de Fora, Campus Governador Valadares (UFJF-GV), MG, Brazil
    Conceived the project Designed the experiments Performed experiments Wrote the manuscript Critically revised the manuscript.
  • Raquel Tognon Ribeiro, Universidade Federal de Juiz de Fora. Universidade Federal de Alfenas. Faculdade de Ciências Farmacêuticas, MG, Brazil
    Conceived the project Designed the experiments Performed experiments Wrote the manuscript Critically revised the manuscript.

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Published

2023-08-28

Issue

Vol. 59 (2023)

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How to Cite

Focal adhesion kinase inhibition decreases cell viability and induces apoptosis of JAK2 V617F positive cells. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, e23075. https://doi.org/10.1590/