Visualizing Antineoplastic Activity with a Whole Organism Drosophila melanogaster Screen

Abstract

Cancer is a disease characterized by high mitosis rates with a loss of regulation. Many antineoplastics, those drugs used to treat cancer, act by slowing or halting mitosis. We are developing a whole-organism screening protocol to identify novel antineoplastics. After exposing Drosophila melanogaster eggs and larva to a compound, their growth rate and population decrease if mitosis inhibition or arrest occur. We screened several compounds from the National Cancer Institutes (NCI) Developmental Therapeutics Program (DTP). Our screen successfully identified two compounds, toyocamycin and stictic acid, previously identified as possible antineoplastics. Toyocamycin killed a fraction of the population proportional to the dose concentration resulting in full mortality at 100 and 200 M. At low doses, toyocamycin also slowed larval development by a mean of one day. RNAseq showed that no genes were differentially expressed in mature flies after toyocamycin exposure was halted. Stictic acid delayed larval growth by an equal or greater margin compared to toyocamycin. These results demonstrate that decreases in Drosophila growth or population can predict a compounds antineoplastic activity and toxicity.