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Pre-clinical evidence that salinomycin is active against retinoblastoma via inducing mitochondrial dysfunction,

Jing Li1, Yao Min2

  • 1Department of Ophthalmology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Wuhan, 430014, Hubei, China.

Journal of Bioenergetics and Biomembranes
|August 8, 2021
PubMed

Insights

Salinomycin shows promise for treating retinoblastoma, a rare eye cancer. This study found salinomycin effectively suppresses tumor growth and induces cell death in retinoblastoma models by targeting mitochondrial function.

Area of Science:

  • Oncology
  • Ophthalmology
  • Molecular Biology

Background:

  • Retinoblastoma treatment outcomes remain poor, necessitating novel therapeutic strategies.
  • Salinomycin exhibits selective anti-cancer properties across various cancer types, making it a potential candidate for retinoblastoma therapy.

Purpose of the Study:

  • To evaluate the efficacy of salinomycin in retinoblastoma models.
  • To elucidate the underlying mechanisms of salinomycin's action in retinoblastoma.

Main Methods:

  • In vitro cellular functional assays were performed.
  • A xenograft retinoblastoma mouse model was utilized for in vivo studies.
  • Biochemical assays focused on mitochondrial function and related signaling pathways.

Main Results:

  • Salinomycin suppressed retinoblastoma cell growth and induced apoptosis, irrespective of cellular heterogeneity.
  • The drug specifically inhibited stem-like and highly invasive cancer cells.
  • In vivo studies demonstrated that non-toxic doses of salinomycin inhibited tumor growth and promoted apoptosis.
  • Mechanistic investigations revealed salinomycin inhibits mitochondrial respiration (Complex I and II), reduces membrane potential, and decreases cellular energy, leading to oxidative stress and activating AMPK/mTOR pathways.

Conclusions:

  • Salinomycin demonstrates significant therapeutic potential against retinoblastoma.
  • The drug's mechanism involves mitochondrial dysfunction and energy depletion.
  • Salinomycin could be a valuable addition to the current retinoblastoma treatment regimen.
Keywords:
AMPK/mTORMitochondria respirationRetinoblastomaSalinomycin

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