A research group led by Professor Atsushi Kuhara, Visiting Researcher Misaki Okahata, and Specially Appointed Research Lecturer Akane Ohta of the Graduate School of Natural Science at Konan University and Researcher Kenji Nakao of Takeda Pharmaceutical Company (at the time of research) has announced that they discovered that anticancer drugs leptomycin B and camptothecin increased the body's cold tolerance using a nematode (C. elegans). They established an experimental system for screening of drugs related to cold tolerance using nematodes in a short period of time and at a low cost. If a similar phenomenon occurs in humans, outcomes of the experiment may help in sustaining life at low temperatures while transporting critically ill patients. The results were published in the international academic journal Scientific Reports on March 5.
About 4,000 chemicals were exposed to the nematode C. elegans to measure cold tolerance. Using the phenomenon that nematodes grown at 22.5℃ cannot survive at 2℃, chemicals that enhance cold tolerance were screened.
Provided by Konan University
(sourced from Okahata et al., Scientific Reports, 14, 5401, 1-14, 2024)
Nematodes are inexpensive to breed and have numerous genes homologous to humans. In this study, nematodes were exposed to approximately 4,000 different drugs one by one to identify the agents that affect cold tolerance, and the cold tolerance of nematodes was surveyed. Transcriptome analysis was performed to determine the genes affected by each drug.
Exposure to leptomycin B under cold stimuli increased the expression of 1166 genes, including those involved in stress response, and decreased the expression of 553 genes. Mutants of cadherin family cdh-10 and divalent cation transporter smf-3, whose expression levels were reduced, showed abnormal cold tolerance. Exposure to camptothecin under cold stimuli increased the expression of 695 genes, including those involved in stress responses, and markedly decreased the expression of 734 genes, including those involved in extracellular substances and transcription factors. Mutants of the alkylglycerol monooxygenase gene agmo-1 and the serine threonine kinase gene sad-1, whose expression levels were reduced, showed abnormal cold tolerance. Furthermore, the insulin receptor DAF-2, which is involved in cold tolerance present in the gut, regulated cold tolerance downstream of leptomycin B or camptothecin.
Kuhara said, "By understanding the cold tolerance mechanisms of C. elegans, we have successfully identified drugs that enhance the body's cold tolerance from a vast array of drugs at a low cost and in a short period of time. Moreover, we were able to identify genes affected by the drugs. Making a drug available clinically requires a great amount of time and money. The experimental system used in this study may be useful for high-throughput basic research, from drug screening to mechanism of action studies.
Journal Information
Publication: Scientific Reports
Title: Screening for cold tolerance genes in C. elegans, whose expressions are affected by anticancer drugs camptothecin and leptomycin B
DOI: 10.1038/s41598-024-55794-z
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.