Open AccessSelective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation
Author(s) -
Rui Tang,
Atsushi Kimishima,
Ryosuke Ishida,
Andi Setiawan,
Masayoshi Arai
Publication year - 2019
Publication title -
natural medicines/journal of natural medicines
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 46
eISSN - 1861-0293
pISSN - 1340-3443
DOI - 10.1007/s11418-019-01357-w
Subject(s) - cytotoxicity , cancer cell , cell culture , apoptosis , biochemistry , pancreatic cancer , biology , cytotoxic t cell , growth inhibition , chemistry , cancer , microbiology and biotechnology , in vitro , genetics
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 IC 50 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.