Quantitative proteomics discloses Monacolin K – induced alterations in Triple Negative Breast Cancer Cells proteome and phosphoproteome
A positive prognosis of triple negative breast cancers can be actually considered as one of the major challenges in clinical; accordingly, scientific research has the mission to find out novel chemotherapeutics to make it curable. In recent times, a good potential of dietary bioactive natural substances, called nutraceuticals, in suppressing cancer cell proliferation thought gene expression regulation has been discovered: this effect and the lack of toxicity make nutraceuticals potentially efficient agents against cancer. Monacolin K from red rice, a FDA-approved and well tolerated compound generally employed to treat hypercholesterolemia, has been proved to have anti-proliferative and apoptotic effects in a wide panel of triple negative breast cancers. Thus, an unbiased analysis of Monacolin K induced MDA-MB 231 cellular pathways alterations has been carried out by quantitative proteomics exploiting isobaric tags. Despite the positive modulation of some proteins already reported in literature, it has been found an interesting increased concentration of the tissue-type plasminogen activator PLAT. This is a marker of good prognosis in mammary cancer, suggesting anti-metastatic properties of this molecule as strongly associated with alterations in cytoskeleton organization and the consequent modulation of adhesion, motility and proteolysis. In accordance, some of the found MNK-induced phosphoproteome alterations have a tight connection to cell migration mechanisms. In this setting, it has been very attractive the over phosphorylation of Lamin A and of Melanophilin induced by MNK. Moreover, MNK effect has been exerted on the over expression of the tissue inhibitor of metalloproteinase-2 (TIMP-2), an endogenous metalloproteinase inhibitor. This protein modulates growth, migration and invasion of tumor cells and inhibits tumor angiogenesis.