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Quantification of hormesis in anticancer-agent dose-responses

Marc A Nascarella1, Edward J Stanek, George R Hoffmann

  • 1Department of Public Health, Environmental Health Sciences Division, University of Massachusetts-Amherst, Amherst, MA, USA. mnascarella@gradientcorp.com

Dose-Response : a Publication of International Hormesis Society
|June 23, 2009
PubMed

Insights

This study analyzed 2,189 anticancer agents in yeast, finding that over half exhibit hormetic dose responses. These findings characterize the quantitative features of hormesis for potential drug development.

Area of Science:

  • Pharmacology and Toxicology
  • Yeast Genetics and Molecular Biology
  • Chemical Biology

Background:

  • Previous research indicated that dose responses below toxic thresholds are often stimulatory.
  • Hormetic dose-response models better explain these stimulatory effects than threshold models.

Purpose of the Study:

  • To quantitatively characterize hormetic concentration-responses for 2,189 candidate anticancer agents in 13 yeast strains.
  • To determine the prevalence of hormesis across diverse chemical classes.

Main Methods:

  • Analysis of quantitative features of 4,548 hormetic concentration-responses using established criteria.
  • Evaluation of 2,189 diverse chemical compounds, including mustards, alkylating agents, and antimetabolites.
  • Testing across 13 strains of Saccharomyces cerevisiae.

Main Results:

  • Over half (52.5%) of the evaluated chemicals displayed hormetic dose responses in at least one yeast strain.
  • Key quantitative features identified include: a 5-fold mean stimulation range, 27% mean maximum stimulation, and a 3.7-fold mean range to the toxic threshold.
  • 24 agents demonstrated hormesis across all 13 yeast strains.

Conclusions:

  • Hormesis is a common dose-response phenomenon among candidate anticancer agents in yeast.
  • The characterized quantitative features provide a basis for understanding and utilizing hormesis in drug discovery.
  • Findings contribute to the broader understanding of hormetic dose-response relationships in chemical biology.
Keywords:
anti-tumorbiphasichormesislow-dosethresholdyeast

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