Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function

Manojit M Swamynathan1,2, Shan Kuang1, Kaitlin E Watrud1

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11771, USA.

Science (New York, N.Y.)
|October 24, 2024
PubMed

Insights

Pro-oxidant vitamin K precursor menadione sodium bisulfite (MSB) suppresses prostate cancer progression in mice. MSB also improved muscle function and lifespan in a myotubular myopathy model.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Antioxidant vitamin E supplements are linked to increased prostate cancer (PC) risk in men.
  • The protective effects of pro-oxidants against PC remain largely unexplored.

Purpose of the Study:

  • To investigate the potential of pro-oxidant vitamin K precursor, menadione sodium bisulfite (MSB), in suppressing PC progression.
  • To elucidate the mechanism of action of MSB in cancer cells and its therapeutic potential in other diseases.

Main Methods:

  • Administration of MSB to mice with induced prostate cancer.
  • Investigating the interaction of MSB with the class III phosphatidylinositol 3-kinase VPS34.
  • Testing MSB in a mouse model of myotubular myopathy caused by MTM1 loss.

Main Results:

  • MSB suppressed prostate cancer progression in mice, inducing oxidative cell death.
  • MSB was found to antagonize VPS34 through oxidation of key cysteines, indicating a redox checkpoint in sorting.
  • Dietary MSB improved muscle histology, function, and lifespan in the myotubular myopathy model.

Conclusions:

  • Pro-oxidant MSB demonstrates therapeutic potential against prostate cancer and myotubular myopathy.
  • The findings highlight a redox checkpoint in cellular sorting regulated by VPS34.
  • Understanding pro-oxidant selectivity opens new avenues for therapeutic development.

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