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Sulforaphane inhibits PRMT5 and MEP50 function to suppress the mesothelioma cancer cell phenotype

Geraldine Ezeka1, Gautam Adhikary1, Sivaveera Kandasamy2

  • 1Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Molecular Carcinogenesis
|April 19, 2021
PubMed

Insights

Sulforaphane (SFN) may treat mesothelioma by targeting Protein arginine methyltransferase 5 (PRMT5) and methylosome protein 50 (MEP50). SFN reduces their levels, suppressing cancer cell aggressiveness and tumor formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Mesothelioma is an aggressive cancer linked to asbestos exposure, with current treatments offering limited success and leading to drug resistance.
  • Protein arginine methyltransferase 5 (PRMT5) and its cofactor methylosome protein 50 (MEP50) are crucial for maintaining cancer cell survival by modifying chromatin and regulating gene expression.

Purpose of the Study:

  • To investigate the role of PRMT5/MEP50 in mesothelioma aggressiveness.
  • To evaluate the potential of sulforaphane (SFN) as a mesothelioma therapeutic agent targeting PRMT5/MEP50.

Main Methods:

  • Studied the impact of PRMT5 or MEP50 loss on mesothelioma cell characteristics.
  • Assessed the effects of SFN treatment on PRMT5/MEP50 levels, histone modifications (H4R3me2s), and cancer cell behavior (spheroid formation, invasion, migration).
  • Evaluated SFN's effect on tumor formation in vivo.

Main Results:

  • Loss of PRMT5 or MEP50 reduced H4R3me2s formation, leading to decreased mesothelioma cell spheroid formation, invasion, and migration.
  • SFN treatment decreased PRMT5/MEP50 levels and H4R3me2s formation, suppressing the aggressive cancer phenotype.
  • SFN treatment reduced tumor formation, correlating with decreased PRMT5/MEP50 expression and activity.

Conclusions:

  • PRMT5/MEP50 are key factors in maintaining the aggressive mesothelioma phenotype.
  • SFN demonstrates potential as a mesothelioma therapeutic agent, partly by inhibiting PRMT5/MEP50 function.
Keywords:
MEP50PRMT5cancer preventionepigenetic regulationmesotheliomasulforaphanetumor suppressor

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