Related Experiment Video
Updated: Nov 29, 2025
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
Published on: October 5, 2020
Revealing the anticancer potential of candidate drugs in vivo using Caenorhabditis elegans mutant strains
Paul Mark Medina1, Jozelle Marie Ponce1, Christian Alfredo Cruz1
1Biological Models Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Metro Manila 1000, Philippines.
Abstract:
Drug repurposing is used as a strategy for finding new drugs for cancer. The process is a faster and a more cost-effective way of providing new indications for drugs that can address emerging drug resistance and numerous side effects of chemotherapeutic drugs. In this study, the in vivo anticancer potential of itraconazole, disulfiram, etodolac, and ouabain were assessed using five different C. elegans mutant strains. Each strain contains mutations in genes involved in different signaling pathways such as Wnt (JK3476), Notch (JK1107 and BS3164), and Ras-ERK (SD939 and MT2124) that result to phenotypes of sterility, infertility, and multivulva formation. These same signaling pathways have been shown to be defective in several human cancer types. The four candidate drugs were tested on the C. elegans mutant strains to determine if they rescue the mutant phenotypes. Both ouabain and etodolac significantly reduced the sterile and infertile phenotypes of JK3476, JK1107, BS3164, and SD939 strains (p=0.0010). Finally, itraconazole and etodolac significantly reduced multivulva formation (p=0.0021). The degrees of significant phenotypic rescues of each mutant were significantly higher than vehicle only (1% DMSO). Therefore, this study demonstrated that the four candidate drugs have anticancer potential in vivo, and etodolac had the highest anticancer potential.
Insights
Drug repurposing offers a faster, cost-effective cancer treatment strategy. Four drugs, including etodolac, showed in vivo anticancer potential by rescuing C. elegans mutant phenotypes.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Drug repurposing accelerates the discovery of new cancer therapies.
- Existing chemotherapeutics often cause side effects and drug resistance.
- Targeting Wnt, Notch, and Ras-ERK pathways is crucial for cancer treatment.
Purpose of the Study:
- To evaluate the in vivo anticancer potential of itraconazole, disulfiram, etodolac, and ouabain.
- To assess drug efficacy in C. elegans models with mutations in cancer-related signaling pathways.
- To identify drugs that can rescue developmental phenotypes associated with cancer pathways.
Main Methods:
- Utilized five C. elegans mutant strains with defects in Wnt, Notch, and Ras-ERK signaling.
- Administered itraconazole, disulfiram, etodolac, and ouabain to mutant strains.
- Quantified the rescue of sterility, infertility, and multivulva formation phenotypes.
Main Results:
- Ouabain and etodolac significantly reduced sterile and infertile phenotypes in multiple strains (p=0.0010).
- Itraconazole and etodolac significantly reduced multivulva formation (p=0.0021).
- Phenotypic rescue by candidate drugs exceeded that of the vehicle control (1% DMSO).
Conclusions:
- The study demonstrates the in vivo anticancer potential of itraconazole, disulfiram, etodolac, and ouabain.
- Etodolac exhibited the highest anticancer potential among the tested drugs.
- Drug repurposing in C. elegans provides a valuable model for identifying novel cancer therapeutics.
