Effects of ADMA on gene expression and metabolism in serum-starved LoVo cells

Sci Rep. 2016 May 16:6:25892. doi: 10.1038/srep25892.

Abstract

Serum starvation is a typical way for inducing tumor cell apoptosis and stress. Asymmetric dimethylarginine (ADMA) is an endogenous metabolite. Our previous study reveals the plasma ADMA level is elevated in colon cancer patients, which can attenuate serum starvation-induced apoptosis in LoVo cells. In current study, we evaluated the effects of ADMA on gene expression and metabolism in serum-starved LoVo cells with gene microarray and metabolomic approaches. Our results indicated that 96 h serum starvation induced comprehensive alterations at transcriptional level, and most of them were restored by ADMA. The main signaling pathways induced by serum starvation included cancers-related pathways, pathways in cell death, apoptosis, and cell cycle etc. Meanwhile, the metabolomic data showed serum-starved cells were clearly separated with control cells, but not with ADMA-treated cells in PCA model. The identified differential metabolites indicated serum starvation significantly suppressed TCA cycle, altered glucose and fatty acids metabolism, as well as nucleic acids metabolism. However, very few differential metabolites were identified between ADMA and serum-starved cells. In summary, our current results indicated serum starvation profoundly altered the gene expression and metabolism of LoVo cells, whereas ADMA could restore most of the changes at transcriptional level, but not at metabolic level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • Culture Media / pharmacology
  • Fatty Acids / metabolism
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks / drug effects*
  • Humans
  • Male
  • Metabolome / drug effects*
  • Metabolomics
  • Nucleic Acids / metabolism
  • Oligonucleotide Array Sequence Analysis / methods

Substances

  • Culture Media
  • Fatty Acids
  • Nucleic Acids
  • N,N-dimethylarginine
  • Arginine