Compounds from the marine sponge Cribrochalina vasculum offer a way to target IGF-1R mediated signaling in tumor cells
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// Ana Zovko 1 , Metka Novak 1 , Petra Hååg 1 , Dimitry Kovalerchick 2 , Teresa Holmlund 1 , Katarina Färnegårdh 3 , Micha Ilan 4 , Shmuel Carmeli 2 , Rolf Lewensohn 1 , Kristina Viktorsson 1 1 Department of Oncology and Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden 2 School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel 3 Science for Life Laboratory, Drug Discovery and Development Platform, Department of Organic Chemistry, Stockholm University, Stockholm, Sweden 4 Department of Zoology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel Correspondence to: Kristina Viktorsson, email: kristina.viktorsson@ki.se Ana Zovko, email: zovko.ana@gmail.com Keywords: sponge, small molecule, natural products, lung cancer, insulin growth factor receptor Received: June 11, 2015 Accepted: June 15, 2016 Published: July 1, 2016 ABSTRACT In this work two acetylene alcohols, compound 1 and compound 2, which were isolated and identified from the sponge Cribrochalina vasculum, and which showed anti-tumor effects were further studied with respect to targets and action mechanisms. Gene expression analyses suggested insulin like growth factor receptor (IGF-1R) signaling to be instrumental in controlling anti-tumor efficacy of these compounds in non-small cell lung cancer (NSCLC). Indeed compounds 1 and 2 inhibited phosphorylation of IGF-1Rβ as well as reduced its target signaling molecules IRS-1 and PDK1 allowing inhibition of pro-survival signaling. In silico docking indicated that compound 1 binds to the kinase domain of IGF-1R at the same binding site as the well known tyrosine kinase inhibitor AG1024. Indeed, cellular thermal shift assay (CETSA) confirmed that C. vasculum compound 1 binds to IGF-1R but not to the membrane localized tyrosine kinase receptor EGFR. Importantly, we demonstrate that compound 1 causes IGF-1Rβ but not Insulin Receptor degradation specifically in tumor cells with no effects seen in normal diploid fibroblasts. Thus, these compounds hold potential as novel therapeutic agents targeting IGF-1R signaling for anti-tumor treatment.
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Eribulin, a truncated synthetic version of halichondrin B, derived from the sponge Halichondria okadai, has clinically potential activity against pretreated metastatic breast cancer cells.
“Eribulin, a truncated synthetic version of halichondrin B, derived from the sponge Halichondria okadai [149], has clinically potential activity against pretreated metastatic breast cancer cells [150,151].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [150]
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- Authors
- Zovko, A., Novak, M., Hååg, P., Kovalerchick, D., Holmlund, T., Färnegårdh, K., Ilan, M., Carmeli, S., Lewensohn, R., & Viktorsson, K.
- Affiliations
- Karolinska Institutet (SE)
- Tel Aviv University (IL)
- Stockholm University (SE)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2016-07-01
- Volume
- 7
- Issue
- 31
- Pages
- 50258-50276
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5226581
- OpenAlex
- W2465258693
- Cited by
- 28
- References
- 54
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 2
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Commission
- Cancerfonden
- Knut och Alice Wallenbergs Stiftelse
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Synthesis and Biological Activity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- marine sponge natural products, IGF1R signaling, non-small cell lung cancer, kinase inhibitors, IRS-1, PDK1, EGFR, cellular thermal shift assay, molecular docking, tumor selectivity, anticancer activity
- MeSH terms
- Animals, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Cell Survival, Fibroblasts, Humans, Lung Neoplasms, Phosphorylation, Porifera, Protein Binding, Receptor, Insulin, Signal Transduction, Gene Expression Regulation, Neoplastic, Receptor, IGF Type 1, Tyrphostins, Receptor Protein-Tyrosine Kinases, Gene Expression Profiling, Cell Line, Tumor, Protein Kinase Inhibitors, Insulin Receptor Substrate Proteins, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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