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Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in

Sang-Hun Kim1, Young-Jun Choi2, Kwang-Youn Kim3

  • 1Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.

Biochemical and Biophysical Research Communications
|April 2, 2016
PubMed

Insights

Salinomycin triggers cancer cell death (apoptosis) and survival mechanisms (autophagy) by generating reactive oxygen species (ROS). Targeting ROS may offer a new cancer therapy strategy.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Salinomycin is a potassium ionophore with reported anticancer activity.
  • Osteosarcoma is a challenging bone cancer with limited treatment options.

Purpose of the Study:

  • To investigate the effects of salinomycin on apoptosis and autophagy in osteosarcoma cells.
  • To explore the role of reactive oxygen species (ROS) in salinomycin-induced cell death and survival pathways.

Main Methods:

  • Flow cytometry was used to analyze apoptosis, autophagy, mitochondrial membrane potential (MMP), and ROS.
  • Western blotting assessed the expression of apoptosis- and autophagy-related proteins.
  • N-acetyl-l-cysteine (NAC) and 3-methyladenine (3-MA) were used to investigate the roles of ROS and autophagy.

Main Results:

  • Salinomycin induced apoptosis in U2OS cells, indicated by MMP changes and caspase cleavage.
  • Salinomycin increased autophagy markers, including acidic vesicular organelles (AVO) accumulation.
  • ROS generation by salinomycin promoted both apoptosis and autophagy, as NAC treatment attenuated these effects.
  • Inhibiting autophagy with 3-MA enhanced salinomycin-induced apoptosis.

Conclusions:

  • Salinomycin induces both apoptosis and autophagy in osteosarcoma cells.
  • ROS plays a crucial role in mediating salinomycin's effects on apoptosis and autophagy.
  • Salinomycin-induced autophagy may act as a survival mechanism, suggesting ROS-targeted therapies could be a potential cancer treatment strategy.
Keywords:
ApoptosisAutophagyReactive oxygen speciesSalinomycinU2OS cells

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