Dropwort-Induced Metabolic Reprogramming Restrains Yap/Taz/Tead Oncogenic Axis Inwards Mesothelioma.

Journal of Experimental & Clinical Cancer Research 2019 August ix [Link]

Pulito C, Korita E, Sacconi A, Valerio M, Casadei L, Lo Sardo F, Mori F, Ferraiuolo M, Grasso G, Maidecchi A, Lucci J, Sudol M, Muti P, Blandino G, Strano S

Abstract

BACKGROUND:

Over the by decade, newly designed cancer therapies convey non significantly improved the survival of patients diagnosed amongst Malignant Pleural Mesothelioma (MPM). Among a express publish of genes that are oft mutated inward MPM several of them encode proteins that belong to the HIPPO tumor suppressor pathway.

METHODS:

The anticancer effects of the summit bloom standardized extract of Filipendula vulgaris (Dropwort) were characterized inward “in vitro” together with “in vivo” models of MPM. At the molecular level, 2 “omic” approaches were used to investigate Dropwort anticancer machinery of action: a metabolomic profiling together with a phosphoarray analysis.

RESULTS:

We institute that Dropwort significantly reduced jail cellular telephone proliferation, viability, migration together with inward vivo tumor increase of MPM jail cellular telephone lines. Notably, Dropwort affected viability of tumor-initiating MPM cells together with synergized amongst Cisplatin together with Pemetrexed inward vitro. Metabolomic profiling revealed that Dropwort handling affected both glycolysis/tricarboxylic acid wheel equally for the decreased consumption of glucose, pyruvate, succinate together with acetate, together with the lipid metabolism. We besides document that Dropwort exerted its anticancer effects, at to the lowest degree partially, promoting YAP together with TAZ poly peptide ubiquitination.

CONCLUSIONS:

Our findings disclose that Dropwort is a promising root of natural compound(s) for targeting the HIPPO pathway amongst chemo-preventive together with anticancer implications for MPM management.



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