Tang, Rui and Kimishima, Atsushi and Ishida, Ryosuke 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. Journal of Natural Medicines, 74 (1). pp. 153-158. ISSN 1861-0293


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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 efects of compound 1 could be mediated by inhibiting complex II in the mitochondrial electron transport chain.

Item Type: Article
Subjects: Q Science > Q Science (General)
Depositing User: Prof Andi Setiawan
Date Deposited: 12 Jan 2022 07:13
Last Modified: 12 Jan 2022 07:13
URI: http://repository.lppm.unila.ac.id/id/eprint/37839

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