Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 19, Pages -Publisher
MDPI
DOI: 10.3390/ijms21197186
Keywords
ezrin; cell migration; cell Invasion; matrix metalloproteinase (MMP)-2; 9 activity; target identification; ent-kaurane diterpenes; proteomics; cancer metastasis
Funding
- Universita degli Studi di Salerno [ORSA189859]
- POR CAMPANIA FESR 2014/2020 Asse 1-Obiettivo specifico 1.2-Azione 1.2. Progetto: Campania OncoTerapie [CUP: B61G18000470007]
- POR FESR 2014/2020 Regione Campania
- System Innovation for Cancer Early Diagnosis-SICED [CUP: B53D18000150007]
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The ent-kaurane diterpene oridonin was reported to inhibit cell migration and invasion in several experimental models. However, the process by which this molecule exerts its anti-metastatic action has not been yet elucidated. In this article, we have investigated the anti-metastatic activity of Oridonin and of one homolog, Irudonin, with the aim to shed light on the molecular mechanisms underlying the biological activity of these ent-kaurane diterpenes. Cell-based experiments revealed that both compounds are able to affect differentiation and cytoskeleton organization in mouse differentiating myoblasts, but also to impair migration, invasion and colony formation ability of two different metastatic cell lines. Using a compound-centric proteomic approach, we identified some potential targets of the two bioactive compounds among cytoskeletal proteins. Among them, Ezrin, a protein involved in the actin cytoskeleton organization, was further investigated. Our results confirmed the pivotal role of Ezrin in regulating cell migration and invasion, and indicate this protein as a potential target for new anti-cancer therapeutic approaches. The interesting activity profile, the good selectivity towards cancer cells, and the lower toxicity with respect to Oridonin, all suggest that Irudonin is a very promising anti-metastatic agent.
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