Top

Published in:

Open Access 01-01-2020 | Original Paper

Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation

Authors: Rui Tang, Atsushi Kimishima, Ryosuke Ishida, Andi Setiawan, Masayoshi Arai

Published in: Journal of Natural Medicines | Issue 1/2020

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.

Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49:6449–6465PubMed

Rohwer N, Cramer T (2011) Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Update 14:191–201CrossRef

Chen S, Rehman SK, Zhang W, Wen A, Yao L, Zhang J (2010) Autophagy is a therapeutic target in anticancer drug resistance. Biochim Biophys Acta 1806:220–229PubMed

Arai M, Kawachi T, Kotoku N, Nakata C, Kamada H, Tsunoda S, Tsutsumi Y, Endo H, Inoue M, Sato H, Kobayashi M (2016) Furospinosulin-1, marine spongean furanosesterterpene, suppresses the growth of hypoxia-adapted cancer cells by binding to transcriptional regulators p54^nrb and LEDGF/p75. ChemBioChem 17:181–189CrossRef

Kawachi T, Tanaka S, Fukuda A, Sumii Y, Setiawan A, Kotoku N, Kobayashi M, Arai M (2019) Target identification of the marine natural products dictyoceratin-A and -C as selective growth inhibitors in cancer cells adapted to hypoxic environments. Mar Drugs 17:E163CrossRef

Arai M, Shin D, Kamiya K, Ishida R, Setiawan A, Kotoku N, Kobayashi M (2017) Marine spongean polybrominated diphenyl ethers, selective growth inhibitors against the cancer cells adapted to glucose starvation, inhibits mitochondrial complex II. J Nat Med 71:44–49CrossRef

Arai M, Kamiya K, Shin D, Matsumoto H, Hisa T, Setiawan A, Kotoku N, Kobayashi M (2016) N-methylniphatyne A, a new 3-alkylpyridine alkaloid as an inhibitor of the cancer cells adapted to nutrient starvation, from an Indonesian marine sponge of Xestospongia sp. Chem Pharm Bull 64:766–771CrossRef

Kotoku N, Ishida R, Matsumoto H, Arai M, Tida K, Setiawan A, Muraoka M, Kobayashi M (2017) Biakamides A–D, unique polyketides from a marine sponge, act as selective growth inhibitors of tumor cells adapted to nutrient starvation. J Org Chem 82:1705–1718CrossRef

Nakano H, Hara M, Meshiro T, Ando K, Saito Y, Morimoto S (1990) Japan Patent Kokai 1990–218686

10.

Yamazaki H, Takahashi O, Murakami K, Namikoshi M (2015) Induced production of a new unprecedented epitrithiodiketopiperazine, chlorotrithiobrevamide, by a culture of the marine-derived Trichoderma cf. brevicompactum with dimethyl sulfoxide. Tetrahedron Lett 56:6262–6265CrossRef

11.

Garo E, Starks CM, Jensen PR, Fenical W, Lobkovsky E, Clardy J (2003) Trichodermamides A and B, cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens. J Nat Prod 66:423–426CrossRef

12.

Liu R, Gu QQ, Zhu WM, Cui CB, Fan GT (2005) Trichodermamide A and aspergillazine A, two cytotoxic modified dipeptides from a marine-derived fungus Spicaria elegans. Arch Pharmacol Res 28:1042–1046CrossRef

13.

Capon RJ, Ratnayake R, Stewart M, Lacey E, Tennant S, Gill JH (2005) Aspergillazines A–E: novel heterocyclic dipeptides from an Australian strain of Aspergillus unilateralis. Org Biomol Chem 3:123–129CrossRef

14.

Momose I, Ohba S, Tatsuda D, Kawada M, Masuda T, Tsujiuchi G, Yamori T, Esumi H, Ikeda D (2010) Mitochondrial inhibitors show preferential cytotoxicity to human pancreatic cancer PANC-1 cells under glucose-deprived conditions. Biochem Biophys Res Commun 392:460–466CrossRef

15.

Jin S, DiPaola RS, Mathew R, White E (2007) Metabolic catastrophe as a means to cancer cell death. J Cell Sci 120:379–383CrossRef

16.

Lee AS (2007) GRP78 Induction in cancer: therapeutic and prognostic implications. Cancer Res 67:3496–3499CrossRef

17.

Xia D, Yu CA, Kim H, Xia JZ, Kachurin AM, Zhang L, Yu L, Deisenhofer J (1997) Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science 277:60–66CrossRef

18.

Weatherly LM, Shim J, Hashmi HN, Kennedy RH, Hess ST, Gosse JA (2016) Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and humanmast cells and in primary human keratinocytes. J Appl Toxicol 36:777–789CrossRef

Title: Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation
Authors: Rui Tang
Atsushi Kimishima
Ryosuke Ishida
Andi Setiawan
Masayoshi Arai
Publication date: 01-01-2020
Publisher: Springer Singapore
Published in: Journal of Natural Medicines / Issue 1/2020
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-019-01357-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice

Evaluation of white Kwao Krua (Pueraria candollei Grah. ex Benth.) products sold in Thailand by molecular, chemical, and microscopic analyses

Sweroside ameliorated carbon tetrachloride (CCl4)-induced liver fibrosis through FXR-miR-29a signaling pathway

Identification and characterization of organic and glycosidic acids in crude resin glycoside fraction from Calystegia hederacea

Consumption of lycopene-rich tomatoes improved glucose homeostasis in rats via an increase in leptin levels

Antiinflammatory constituents of Atractylodes chinensis rhizome improve glomerular lesions in immunoglobulin A nephropathy model mice