Elimination of stem-like cancer cell side-population by auranofin through modulation of ROS and glycolysis

Area of Science:

• Oncology
• Cancer Stem Cell Biology
• Pharmacology

Background:

• Cancer side-population (SP) cells are stem-like cells crucial for drug resistance via ABCG2 transporter activity.
• Auranofin (AF), used for rheumatoid arthritis, exhibits anti-tumor properties, but its effect on SP cells is unknown.

Purpose of the Study:

• To investigate the impact of Auranofin on cancer side-population cells.
• To explore the mechanisms underlying Auranofin's effects.
• To evaluate the synergistic potential of Auranofin with chemotherapy.

Main Methods:

• Assessed Auranofin's effect on SP cell depletion and stem cell marker expression.
• Investigated the role of reactive oxygen species (ROS) and antioxidant N-acetylcysteine (NAC).
• Examined Auranofin's impact on cellular ATP levels, glycolysis, and ABCG2 function.
• Evaluated the combination therapy of Auranofin and adriamycin in vitro and in vivo.

Main Results:

• Auranofin significantly depleted SP cells and downregulated stem cell markers in lung cancer cells.
• AF-induced SP cell depletion was mediated by ROS and reversed by NAC.
• AF caused ATP depletion by inhibiting glycolysis, potentially impairing ABCG2 function and enhancing drug accumulation.
• Combination of AF and adriamycin demonstrated synergistic anti-cancer effects in vitro and in vivo.

Conclusions:

• Auranofin effectively targets and depletes cancer stem-like SP cells.
• Simultaneous ROS increase and glycolysis inhibition represent a novel strategy against stem-like cancer cells.
• Combination therapy with Auranofin and adriamycin shows promise for enhanced cancer treatment efficacy.