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Combined Transcriptomics and Chemical-Genetics Reveal Molecular Mode of Action of Valproic acid, an Anticancer

Upendarrao Golla1, Deepthi Joseph1, Raghuvir Singh Tomar1

  • 1Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, 462066, India.

Scientific Reports
|October 14, 2016
PubMed

Insights

Valproic acid (VA), an anticancer agent, impacts numerous cellular processes like DNA repair and metabolism. This study in yeast reveals VA

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Valproic acid (VA) is a histone deacetylase inhibitor with emerging anticancer properties.
  • The precise molecular mechanisms underlying VA's diverse cellular effects remain largely unelucidated.

Purpose of the Study:

  • To comprehensively identify cellular processes and molecular targets affected by VA in vivo.
  • To utilize budding yeast as a model organism for dissecting VA's molecular actions.

Main Methods:

  • Genome-wide transcriptome analysis to assess gene expression changes induced by VA.
  • Functional enrichment analysis to categorize affected cellular pathways.
  • Genetic screening to identify VA molecular targets and essential pathways.

Main Results:

  • VA treatment significantly altered the expression of approximately 30% of the yeast genome.
  • Affected processes include cell cycle, DNA repair, stress response, metabolism, and ion homeostasis.
  • Activation of mitogen-activated protein kinases (MAPKs) Hog1 and Slt2 was observed; VA's effects were mitigated in lipid particle-deficient cells.

Conclusions:

  • This study deciphers novel molecular insights into VA's diverse cellular effects.
  • Identified VA targets and affected pathways offer potential therapeutic strategies and detoxification approaches.

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