Eudistomin C, an Antitumor and Antiviral Natural Product, Targets 40S Ribosome and Inhibits Protein Translation

Ota, Yu; Chinen, Takumi; Yoshida, Keisuke; Kudo, S.; Nagumo, Yoko; Shiwa, Yuh; Yamada, R.; Umihara, Hirotatsu; Iwasaki, Kotaro; Masumoto, Hiroshi; Yokoshima, Satoshi; Yoshikawa, Hideki; Fukuyama, Tohru; Kobayashi, Jun’ichi; Usui, Takeo

doi:10.1002/cbic.201600075

Cited by 16 publications

(11 citation statements)

References 15 publications

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“…714 A yeast-based chemical genetics approach was used to identify the cellular target of eudistomin C as being the uS11containing ribosomal subunit and that it is a potent inhibitor of protein translation. 715 Eudistomin U is a weak DNA binder. 716…”

Section: Tunicates (Ascidians)mentioning

confidence: 99%

Marine natural products

et al. 2018

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Covering: 2016. Previous review: Nat. Prod. Rep., 2017, 34, 235-294This review covers the literature published in 2016 for marine natural products (MNPs), with 757 citations (643 for the period January to December 2016) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1277 in 432 papers for 2016), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included.

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Section: Tunicates (Ascidians)mentioning

confidence: 99%

Marine natural products

et al. 2018

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“…To distinguish the effect of EudiC on uS11, we performed biochemical analysis using biotinylated EudiC and purified ribosome complexes. Because biotinylated EudiC failed to pull Fap7p down and no effect on 18S maturation processes was observed, it was confirmed that EudiC targets the matured 40S ribosome and inhibits protein translation but not rRNA maturation [50].…”

Section: Application 2: Target Idmentioning

confidence: 86%

“…In this review, we discuss the construction of two multidrug-sensitive yeast strains, 12geneΔHSR [48] and 12geneΔHSR-iERG [49], which are available for genetic analysis. We also discuss the application of these strains in drug screening and target ID [50].…”

Section: Saccharomyces Cerevisiae a Useful Model Organism For Chemicmentioning

confidence: 99%

“…Since our strains show multidrug sensitivity without a decrease in genetic availability, they should also be useful for performing target ID for drugs and the mechanism evaluation of compounds, especially those which are only available in limited amounts, such as natural products. Here we show an example of target ID [50]. Eudistomin C (EudiC, Figure 8), a natural product isolated from the Caribbean tunicate Eudistoma olivaceum [74,75] shows broadspectrum antiviral activity [76].…”

Section: Application 2: Target Idmentioning

confidence: 99%

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Multidrug Sensitive Yeast Strains, Useful Tools for Chemical Genetics

Chinen¹,

Hamada²,

Taguchi³

et al. 2018

The Yeast Role in Medical Applications

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The budding yeast Saccharomyces cerevisiae is a useful eukaryote model organism for application to chemical biology studies, for example, drug screening, drug evaluation, and target identification. To use yeast for chemical biology research, however, it has been necessary to construct yeast strains suitable for various compounds because of their high drug resistance. Hence, the deletion of all multidrug resistance genes except for those that are important for viability and for genetic experiments/manipulation could increase the drug sensitivity without influencing the transformation, mating, or sporulation efficiency. There are two major factors conferring multidrug resistance in S. cerevisiae: one is the drug efflux system and the other is the permeability barrier. We therefore constructed a strain which shows high sensitivity to multiple drugs by disrupting the drug efflux system using ATP-binding cassette transporters and suppressing the membrane barrier system by introducing an ERG6-inducible system. In this review, we discuss the construction of our multidrug-sensitive yeast strains and their application in chemical biology.

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“…They were originally isolated by Rinehart's group [81] from the Caribbean tunicate Eudistoma olivaceum. Eudistomin C is found to exert antitumoral and antiviral activity, targeting the 40S ribosome subunit and inhibiting protein translation [110]. Eudistomin inhibited in vivo tumor growth of murine leukemia P338 allografts when injected i.p.…”

Section: Tunicatesmentioning

confidence: 99%

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds

et al. 2020

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The marine environment represents an outstanding source of antitumoral compounds and, at the same time, remains highly unexplored. Organisms living in the sea synthesize a wide variety of chemicals used as defense mechanisms. Interestingly, a large number of these compounds exert excellent antitumoral properties and have been developed as promising anticancer drugs that have later been approved or are currently under validation in clinical trials. However, due to the high need for these compounds, new methodologies ensuring its sustainable supply are required. Also, optimization of marine bioactives is an important step for their success in the clinical setting. Such optimization involves chemical modifications to improve their half-life in circulation, potency and tumor selectivity. In this review, we outline the most promising marine bioactives that have been investigated in cancer models and/or tested in patients as anticancer agents. Moreover, we describe the current state of development of anticancer marine compounds and discuss their therapeutic limitations as well as different strategies used to overcome these limitations. The search for new marine antitumoral agents together with novel identification and chemical engineering approaches open the door for novel, more specific and efficient therapeutic agents for cancer treatment.

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Eudistomin C, an Antitumor and Antiviral Natural Product, Targets 40S Ribosome and Inhibits Protein Translation

Cited by 16 publications

References 15 publications

Marine natural products

Marine natural products

Multidrug Sensitive Yeast Strains, Useful Tools for Chemical Genetics

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds

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