Realgar bioleaching solution is a less toxic arsenic agent in suppressing the Ras/MAPK pathway in Caenorhabditis elegans

Environ Toxicol Pharmacol. 2013 Mar;35(2):292-9. doi: 10.1016/j.etap.2013.01.001. Epub 2013 Jan 10.

Abstract

To explore other arsenic derivatives with anticancer effects and fewer adverse effects, realgar bioleaching solution (RBS) has been found to be a viable approach. Here we used C. elegans as a model organism to its possible efficacy for anti-cancer effect of RBS. Our results indicated that RBS significantly suppressed the multivulva (Muv) phenotype of let-60 ras(gf) mutant that was positive correlated to arsenic concentrations in worms and also inhibited Muv phenotype of lin-15(lf) upstream of Ras/MAPK pathway, but did not affect the Muv phenotype resulting from loss-of-function mutations of lin-l(lf) downstream of Ras/MAPK pathway, which may be mechanism-based. In toxicity tests, RBS did not lead to reduction resulting from arsenic trioxide (ATO) in the number of pharyngeal pumping which was orthologous to vertebrate heart beating in wild type C. elegans. Overall, RBS was likely to be a potential anti-cancer drug candidate with high efficiency and low toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenicals
  • Body Size / drug effects
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Larva / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Mutation
  • Pharynx / drug effects
  • Pharynx / physiology
  • Phenotype
  • Solutions
  • Sulfides / toxicity*
  • Toxicity Tests / methods
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Arsenicals
  • Caenorhabditis elegans Proteins
  • Solutions
  • Sulfides
  • Transcription Factors
  • lin-15A protein, C elegans
  • let-60 protein, C elegans
  • arsenic disulfide
  • ras Proteins