Cardiac glycosides block cancer growth through HIF-1α- and NF-κB-mediated Plk1

Area of Science:

• Molecular Biology
• Cell Biology
• Cancer Research

Background:

• Cardiac glycosides inhibit the sodium/potassium adenosine triphosphatase (sodium pump).
• Previous studies suggest cardiac glycosides induce G2/M phase arrest in cancer cells.
• Mechanisms of cardiac glycoside-induced cell cycle arrest remain largely unknown.

Purpose of the Study:

• To investigate the detailed mechanisms of cardiac glycoside-induced mitotic arrest.
• To identify key molecular targets involved in the anticancer effects of cardiac glycosides.

Main Methods:

• Utilized live-cell imaging to observe bufalin-treated cancer cells.
• Assessed the expression levels of polo-like kinase 1 (Plk1).
• Investigated the role of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-κB) in bufalin's mechanism.

Main Results:

• Bufalin and other cardiac glycosides induce mitotic arrest by downregulating Plk1 expression.
• Bufalin treatment causes delays in prophase entry, prometaphase arrest, or apoptosis.
• Bufalin and sodium pump knockdown reduce Plk1 expression via downregulation of HIF-1α and NF-κB.

Conclusions:

• Cardiac glycosides induce mitotic arrest and apoptosis through HIF-1α- and NF-κB-mediated downregulation of Plk1.
• HIF-1α and NF-κB are critical targets for the anticancer action of cardiac glycosides.
• These findings elucidate the molecular pathways underlying cardiac glycoside-mediated cancer growth inhibition.