Background: Over the past decade, newly designed cancer therapies have not significantly improved the survival of patients diagnosed with Malignant Pleural Mesothelioma (MPM). Among a limited number of genes that are frequently mutated in MPM several of them encode proteins that belong to the HIPPO tumor suppressor pathway. Methods: The anticancer effects of the top flower standardized extract of Filipendula vulgaris (Dropwort) were characterized in "in vitro" and "in vivo" models of MPM. At the molecular level, two "omic" approaches were used to investigate Dropwort anticancer mechanism of action: a metabolomic profiling and a phosphoarray analysis. Results: We found that Dropwort significantly reduced cell proliferation, viability, migration and in vivo tumor growth of MPM cell lines. Notably, Dropwort affected viability of tumor-initiating MPM cells and synergized with Cisplatin and Pemetrexed in vitro. Metabolomic profiling revealed that Dropwort treatment affected both glycolysis/tricarboxylic acid cycle as for the decreased consumption of glucose, pyruvate, succinate and acetate, and the lipid metabolism. We also document that Dropwort exerted its anticancer effects, at least partially, promoting YAP and TAZ protein ubiquitination. Conclusions: Our findings reveal that Dropwort is a promising source of natural compound(s) for targeting the HIPPO pathway with chemo-preventive and anticancer implications for MPM management.
Dropwort-induced metabolic reprogramming restrains YAP/TAZ/TEAD oncogenic axis in mesothelioma / C. Pulito, E. Korita, A. Sacconi, M. Valerio, L. Casadei, F. Lo Sardo, F. Mori, M. Ferraiuolo, G. Grasso, A. Maidecchi, J. Lucci, M. Sudol, P. Muti, G. Blandino, S. Strano. - In: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH. - ISSN 1756-9966. - 38:1(2019 Aug 09), pp. 349.1-349.22.
|Titolo:||Dropwort-induced metabolic reprogramming restrains YAP/TAZ/TEAD oncogenic axis in mesothelioma|
|Parole Chiave:||Cancer metabolism; HIPPO tumour suppressor pathway; Mesothelioma; Phytonutrient; YAP; Animals; Cell Cycle Proteins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Disease Models, Animal; Energy Metabolism; Filipendula; Humans; Lung Neoplasms; Mesothelioma; Mice; Plant Extracts; Protein Binding; Transcription Factors|
|Settore Scientifico Disciplinare:||Settore MED/01 - Statistica Medica|
|Data di pubblicazione:||9-ago-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1186/s13046-019-1352-3|
|Appare nelle tipologie:||01 - Articolo su periodico|