Disease relevance of Cytostatin

• Cytostatin, a novel inhibitor of cell adhesion to components of extracellular matrix produced by Streptomyces sp. MJ654-NF4. II. Physico-chemical properties and structure determination [1].
• Though cytostatin did not inhibit EL-4 cell adhesion to ECM components such as laminin and fibronectin; it inhibited the adhesion of B16 melanoma cells to laminin and collagen type IV but not to fibronectin [2].
• Inhibitory effect of cytostatin on spontaneous lung metastases of B16-BL6 melanoma cells [3].
• We report here that cytostatin (CTS), a novel specific inhibitor of protein phosphatase (PP) 2A, can inhibit B16 melanoma pulmonary metastasis by the expansion and activation of NK cells [4].

High impact information on Cytostatin

• A model of cytostatin bound to the active site of PP2A is presented, compared to that of fostriecin, which is also presented in detail for the first time, and used to provide insights into the role of the key substituents [5].
• Cytostatin has anti-metastatic properties and induces apoptosis [6].
• On the other hand, in EL-4 cells cyclins D1, E, A, and B1 were decreased by strongly apoptosis-inducing cytostatin prior to apoptosis commitment, but neither cyclin A nor B1 was decreased by weakly apoptosis-inducing bactobolin [7].
• In B16 cells, cyclins E, A, and B1 were decreased by strongly apoptosis-inducing bactobolin prior to apoptosis commitment, but cyclin E was not decreased by weakly apoptosis-inducing cytostatin [7].
• Cytostatin, a novel inhibitor of cell adhesion to components of extracellular matrix produced by Streptomyces sp. MJ654-NF4. I. Taxonomy, fermentation, isolation and biological activities [2].

Anatomical context of Cytostatin

• CTS administration in vivo increased mRNA expression of Flt-3 ligand, one of NK-generating cytokines, in bone marrow cells [4].
• These results indicate that cytostatin inhibits cell adhesion through modification of focal contact proteins such as paxillin by inhibiting a PP2A type protein serine/threonine phosphatase [8].

Associations of Cytostatin with other chemical compounds

• Furthermore, cytostatin increased intracellular serine/threonine-phosphorylated proteins and was found to be a selective inhibitor of protein phosphatase 2A (PP2A) [8].

Gene context of Cytostatin

• Alkaline phosphatase treatment diminished cytostatin-induced slow-migrating paxillin [8].
• On the contrary, dephosphocytostatin, a cytostatin analogue, without inhibitory effect on PP2A did not affect B16 cell adhesion including FAK and paxillin [8].
• While the amount of FAK was not affected by cytostatin, electrophoretically slow-migrating paxillin appeared [8].

Analytical, diagnostic and therapeutic context of Cytostatin

• The effect of cytostatin on apoptosis induction was confirmed by means of the ELISA system [9].

References