Methionine Deprivation-induced Cancer Cell Death and Methylation Changes in Key Genes and Gene Promoters of Prostate

Yatin Srinivash Ramesh Babu1, Kallidaikurichi V Venkatachalam2

  • 1College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, U.S.A.

Anticancer Research
|August 1, 2025
PubMed
Abstract

Insights

Targeting methionine metabolism with MEGL gene therapy induces prostate cancer cell death. This approach offers a novel strategy for cancer treatment by selectively depriving cancer cells of a key nutrient.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Cancer cells exhibit dysregulated growth compared to normal cells.
  • Limited uniform treatments exist for effective cancer cure.
  • Prostate cancer cells rely on specific nutrients for survival.

Purpose of the Study:

  • To investigate the effect of methionine deprivation on prostate cancer cell death.
  • To analyze alterations in DNA methylation patterns in prostate cancer cells.
  • To evaluate the efficacy of MEGL-targeted gene therapy.

Main Methods:

  • Transfection of PC3 and other cell lines with MEGL gene constructs for cytoplasmic or nuclear expression.
  • Assessment of cell death using MTT assay.
  • Whole-methylome sequencing of PC3 and DU145 cells to analyze DNA methylation changes.
  • Analysis of key cell-cycle progression genes.

Main Results:

  • MEGL expression induced significant cancer cell death, comparable to methotrexate.
  • Propargylglycine, a MEGL inhibitor, abolished MEGL-mediated cell death.
  • Methylome analysis revealed altered methylation patterns in key genes, including SKA1, ORC6L, BUB1B, PBK, BIRC5, CENPM, TOP2A, and MCM10.

Conclusions:

  • Methionine deprivation via MEGL-targeted gene therapy is a potential strategy for inducing cancer cell death.
  • This approach offers a novel therapeutic avenue compared to conventional treatments.
  • Further research is warranted to explore MEGL's role in cancer therapy.

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