RRC ID 62910
Author Tang R, Zhou D, Kimishima A, Setiawan A, Arai M.
Title Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation.
Journal J Antibiot (Tokyo)
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.
Volume 73(12)
Pages 873-875
Published 2020-12-1
DOI 10.1038/s41429-020-0340-3
PII 10.1038/s41429-020-0340-3
PMID 32587348
MeSH Antineoplastic Agents / chemistry Antineoplastic Agents / isolation & purification* Antineoplastic Agents / pharmacology Aquatic Organisms / chemistry Cell Line, Tumor Cytotoxins / chemistry Cytotoxins / isolation & purification* Cytotoxins / pharmacology Electron Transport / drug effects Humans Molecular Structure Oxygen Consumption / drug effects Paecilomyces / chemistry* Pancreatic Neoplasms / drug therapy* Piperazines / chemistry Piperazines / isolation & purification Piperazines / pharmacology Tumor Microenvironment / drug effects
IF 2.668
Human and Animal Cells PANC-1(RCB2095)