Tang, Rui and Kimishima, Atsushi and Ryosuke, Ishida and Setiawan, Andi and Arai, Masayoshi Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation. Springer Verlag.

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Official URL: https://pubmed.ncbi.nlm.nih.gov/31435860/


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.

Item Type: Other
Subjects: Q Science > Q Science (General)
Depositing User: Prof Andi Setiawan
Date Deposited: 18 Feb 2022 01:19
Last Modified: 18 Feb 2022 01:19
URI: http://repository.lppm.unila.ac.id/id/eprint/39449

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