Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer

Libério, Michelle S., Sadowski, Martin, Nelson, Colleen C., & Davis, Rohan A. (2014) Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer. Marine Drugs, 12(10), pp. 5222-5239.

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Abstract

Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC50 of 5 μM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.

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ID Code: 77864
Item Type: Journal Article
Refereed: Yes
Keywords: ascidian, eusynstyelamide B, cytotoxic, MDA-MB-231, RTCA, G2/M arrest, anticancer drugs, natural products, marine compounds
DOI: 10.3390/md12105222
ISSN: 1660-3397
Subjects: Australian and New Zealand Standard Research Classification > CHEMICAL SCIENCE (030000) > MEDICINAL AND BIOMOLECULAR CHEMISTRY (030400) > Biologically Active Molecules (030401)
Australian and New Zealand Standard Research Classification > CHEMICAL SCIENCE (030000) > MEDICINAL AND BIOMOLECULAR CHEMISTRY (030400) > Characterisation of Biological Macromolecules (030403)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Biochemistry and Cell Biology not elsewhere classified (060199)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Therapy (excl. Chemotherapy and Radiation Therapy) (111204)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Molecular Targets (111207)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 by the authors; licensee MDPI, Basel, Switzerland.
Copyright Statement: This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/4.0/).
Deposited On: 20 Oct 2014 22:47
Last Modified: 02 Dec 2014 23:11

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