Related Experiment Videos
Butyrate and phenylacetate as differentiating agents: practical problems and opportunities
1Irving Weinstein Laboratory for Gastrointestinal Cancer Prevention, Gastroenterology and Nutrition Science, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Journal of Cellular Biochemistry. Supplement
|January 1, 1995
Summary
Differentiating agents like butyrate and phenylacetate can normalize transformed cells. Promising prodrugs, tributyrin and phenylbutyrate, offer therapeutic potential, especially with retinoids for diseases like leukemia.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Differentiating agents alter abnormal cell lines in vitro towards a normal state.
- In vivo studies of agents like butyrate are limited by rapid metabolism.
- Prodrugs offer improved in vivo stability and therapeutic potential.
Purpose of the Study:
- To explore the potential of butyrate and phenylacetate prodrugs as differentiating agents.
- To investigate synergistic effects between differentiating agents and retinoids.
- To identify potential therapeutic and chemopreventive applications for these agents.
Main Methods:
- In vitro studies of butyrate, phenylacetate, and their prodrugs.
- In vivo studies in mice and rats using tributyrin (a butyrate prodrug).
- Evaluation of synergy with retinoic acid and vitamin D analogues.
Main Results:
- Tributyrin, a butyrate prodrug, achieves prolonged serum levels in rodents.
- Butyrate and its derivatives show synergy with retinoic acid in vitro.
- Phenylbutyrate, a phenylacetate prodrug, is a more acceptable alternative.
Conclusions:
- Effective prodrugs like tributyrin and phenylbutyrate enhance therapeutic opportunities.
- Synergy in vivo with retinoids or deltanoids could expand applications.
- Potential targets include leukemias, thalassemia, and sickle cell anemia.