RRC ID 58023
Author Tang R, Kimishima A, Ishida R, Setiawan A, Arai M.
Title Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation.
Journal J Nat Med
Abstract The core of solid tumors is characterized by hypoxia and a nutrient-starved microenvironment and has gained much attention as targets of anti-cancer drugs. In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, epidithiodiketopiperazine DC1149B (1) together with structurally related compounds, trichodermamide A (2) and aspergillazine A (3), were isolated from culture extract of marine-derived Trichoderma lixii. Compounds 1 exhibited potent selective cytotoxic activity against human pancreatic carcinoma PANC-1 cells cultured under glucose-starved conditions with IC50 values of 0.02 µM. The selective index of the compound 1 was found to be 35,500-fold higher for cells cultured under glucose-starved conditions than those under the general culture conditions. The mechanistic analysis indicated that compound 1 inhibited the response of the ER stress signaling. In addition, these effects of compound 1 could be mediated by inhibiting complex II in the mitochondrial electron transport chain.
Volume 74(1)
Pages 153-158
Published 2020-1-1
DOI 10.1007/s11418-019-01357-w
PII 10.1007/s11418-019-01357-w
PMID 31435860
PMC PMC7946679
MeSH Antineoplastic Agents / pharmacology* Cell Line, Tumor Dipeptides / chemistry Dipeptides / pharmacology* Electron Transport / drug effects Glucose / metabolism Growth Inhibitors / pharmacology Humans Mitochondria / metabolism Neoplasms / drug therapy* Piperazines / pharmacology* Trichoderma / chemistry* Tumor Microenvironment
IF 2.055
Times Cited 4
Human and Animal Cells PANC-1(RCB2095)