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Digoxin exerts anticancer activity on human nonsmall cell lung cancer cells by blocking PI3K/Akt pathway

Yingying Wang1, Yongqiang Hou1, Lanjiao Hou1

  • 1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmaceutical Sciences, Tianjin Medical University, Tianjin 300070, China.

Bioscience Reports
|September 22, 2021
PubMed

Insights

Digoxin, a heart failure drug, shows promise in fighting non-small cell lung cancer. It inhibits cancer cell growth, migration, and invasion, suggesting potential as a novel lung cancer therapy.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Lung cancer is a leading cause of cancer mortality due to its metastatic potential.
  • Repurposing existing drugs offers a faster route to novel cancer therapies.

Purpose of the Study:

  • To investigate the antitumor effects of digoxin, a cardiac drug, on non-small cell lung cancer (NSCLC) cell lines.
  • To explore digoxin's impact on cancer cell proliferation, cell cycle, apoptosis, and metastasis.

Main Methods:

  • Treatment of A549 and H1299 NSCLC cell lines with digoxin.
  • Assessment of cell proliferation, colony formation, cell cycle progression, apoptosis, migration, and invasion.
  • Analysis of autophagy markers and the PI3K/Akt signaling pathway.

Main Results:

  • Digoxin inhibited proliferation and colony formation in both cell lines.
  • Cell cycle arrest occurred at G0/G1 (A549) and G2/M (H1299) phases.
  • Digoxin induced mitochondria-mediated apoptosis in A549 cells and autophagy in both cell lines.
  • Metastasis-related processes including migration, invasion, and epithelial-mesenchymal transition were suppressed.
  • Digoxin reduced phosphorylation of Akt, mTOR, and p70S6K in the PI3K/Akt pathway.

Conclusions:

  • Digoxin exhibits significant antitumor activity against non-small cell lung cancer cells in vitro.
  • The drug affects key cancer hallmarks including proliferation, metastasis, and survival pathways.
  • Digoxin demonstrates potential as a therapeutic agent for human non-small cell lung cancer, warranting further investigation.
Keywords:
autophagydigoxinmetastasisnonsmall cell lung cancerproliferation

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