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Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation
- Source :
- Journal of Natural Medicines
- Publication Year :
- 2019
- Publisher :
- Springer Singapore, 2019.
-
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.
- Subjects :
- genetic structures
Antineoplastic Agents
behavioral disciplines and activities
01 natural sciences
Trichoderma lixii
Piperazines
Electron Transport
Cell Line, Tumor
Neoplasms
medicine
Tumor Microenvironment
Cytotoxic T cell
Humans
Cancer
Starvation
Trichoderma
Original Paper
010405 organic chemistry
Chemistry
Correction
Dipeptides
Epidithiodiketopiperazine
Hypoxia (medical)
medicine.disease
Electron transport chain
DC1149B
Growth Inhibitors
0104 chemical sciences
Mitochondria
010404 medicinal & biomolecular chemistry
Glucose
nervous system
Biochemistry
Cancer cell
Unfolded protein response
Molecular Medicine
Marine-derived Trichoderma lixii
medicine.symptom
psychological phenomena and processes
Glucose starvation
Subjects
Details
- Language :
- English
- ISSN :
- 18610293 and 13403443
- Volume :
- 74
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Natural Medicines
- Accession number :
- edsair.doi.dedup.....012521d5de24ce4d99e40604ea8e0987