Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation
- 25 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in The Journal of Antibiotics
- Vol. 73 (12), 873-875
- https://doi.org/10.1038/s41429-020-0340-3
Abstract
The cancer cells that are adapted to the hypoxic and nutrient-starved conditions of the tumor microenvironment have become a key target for anticancer therapies. In the course of search for selective cytotoxic substances against cancer cells adapted to nutrient starvation, (3S,6S)-3,6-dibenzylpiperazine-2,5-dione (1) was isolated from culture extract of marine-derived Paecilomyces formous 17D47-2. Compound 1 showed cytotoxic activity on the human pancreatic carcinoma PANC-1 cells adapted to glucose-starved conditions with IC50 value of 28 µM, whereas no effect was observed against PANC-1 cells under general culture conditions up to 1000 µM. Further studies on the mechanism of the selective cytotoxicity of 1 against the glucose-starved PANC-1 cells suggest that it may function via uncoupling of mitochondrial oxidative phosphorylation.Keywords
Funding Information
- Japan Agency for Medical Research and Development (JP20am0101084)
- MEXT | Japan Society for the Promotion of Science (18H02096, 17H04645)
- Kobayashi International Scholarship Foundation
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