Nelfinavir inhibits proliferation and induces DNA damage in thyroid cancer cells

Kirk Jensen1, Athanasios Bikas2, Aneeta Patel3

  • 1Department of PediatricsUniformed Services University of the Health Sciences, Bethesda, Maryland, USA kirk.jensen@usuhs.edu.

Endocrine-Related Cancer
|February 1, 2017
PubMed

Insights

The HIV protease inhibitor Nelfinavir (NFV) inhibits thyroid cancer cell proliferation and induces DNA damage. NFV shows potential as a novel therapeutic agent for thyroid cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Thyroid cancers are a significant health concern with limited therapeutic options.
  • Emerging research highlights the role of PI3K/AKT and MAPK/ERK signaling pathways in thyroid cancer progression.
  • Nelfinavir (NFV), an HIV protease inhibitor, targets these pathways and presents a potential therapeutic avenue.

Purpose of the Study:

  • To investigate the efficacy of Nelfinavir (NFV) against various thyroid cancer cell lines (follicular, papillary, and anaplastic).
  • To elucidate the mechanisms underlying NFV's effects on thyroid cancer cell proliferation, cell cycle, DNA damage, and apoptosis.
  • To assess NFV's impact on molecular markers of epithelial-mesenchymal transition (EMT) and cancer cell migration.

Main Methods:

  • Utilized FTC133, BCPAP, and SW1736 thyroid cancer cell lines for in vitro studies.
  • Assessed cell proliferation using real-time microscopy and flow cytometry.
  • Determined DNA damage, apoptosis, and EMT marker expression via Western blot and real-time PCR.

Main Results:

  • NFV treatment (10 µM) arrested the cell cycle, increased DNA fragmentation, and induced markers of DNA damage (γH2AX, p53BP1).
  • NFV (20 µM) triggered caspase-3 cleavage, indicating apoptosis, and reduced AKT signaling in PTEN-deficient cells.
  • NFV inhibited migration and survival in non-adherent conditions without affecting EMT markers.

Conclusions:

  • Nelfinavir effectively inhibits proliferation and induces DNA damage in diverse thyroid cancer cell lines.
  • NFV demonstrates potential as a novel therapeutic agent for thyroid cancer treatment.
  • Further in vitro and in vivo studies are warranted to explore NFV's therapeutic potential.

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