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The anticancer phytochemical rocaglamide inhibits Rho GTPase activity and cancer cell migration

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Item Type:Article
Title:The anticancer phytochemical rocaglamide inhibits Rho GTPase activity and cancer cell migration
Creators Name:Becker, M.S. and Müller, P.M. and Bajorat, J. and Schroeder, A. and Giaisi, M. and Amin, E. and Ahmadian, M.R. and Rocks, O. and Köhler, R. and Krammer, P.H. and Li-Weber, M.
Abstract:Chemotherapy is one of the pillars of anti-cancer therapy. Although chemotherapeutics cause regression of the primary tumor, many chemotherapeutics are often shown to induce or accelerate metastasis formation. Moreover, metastatic tumors are largely resistant against chemotherapy. As more than 90% of cancer patients die due to metastases and not due to primary tumor formation, novel drugs are needed to overcome these shortcomings. In this study, we identified the anticancer phytochemical Rocaglamide (Roc-A) to be an inhibitor of cancer cell migration, a crucial event in metastasis formation. We show that Roc-A inhibits cellular migration and invasion independently of its anti-proliferative and cytotoxic effects in different types of human cancer cells. Mechanistically, Roc-A treatment induces F-actin-based morphological changes in membrane protrusions. Further investigation of the molecular mechanisms revealed that Roc-A inhibits the activities of the small GTPases RhoA, Rac1 and Cdc42, the master regulators of cellular migration. Taken together, our results provide evidence that Roc-A may be a lead candidate for a new class of anticancer drugs that inhibit metastasis formation.
Keywords:Flavaglines, Rocaglamide, Cell Migration, Rho GTPase
Source:Oncotarget
ISSN:1949-2553
Publisher:Impact Journals (U.S.A.)
Volume:7
Number:32
Page Range:51908-51921
Date:9 August 2016
Official Publication:https://doi.org/10.18632/oncotarget.10188
PubMed:View item in PubMed

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