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Cytostatin is a natural antitumor inhibitor of cell adhesion to extracellular matrix, blocking adhesion of B16 melanoma cells to laminin and collagen type IV in vitro (IC50s = 1.3 and 1.4 μg/ml, respectively) and B16 cells metastatic activity in mice.1,2 It induces apoptosis of FS3 mouse fibrosarcoma cells (IC50 = 3.1 μg/ml).3 Cytostatin potently and selectively inhibits protein phosphatase 2A (PP2A; IC50 = 29 nM against the catalytic subunit), while having no effect against PP1, PP2B, or PP5.4,5 | [storage]
Store at -20°C | [References]
1. Amemiya, M., Ueno, M., Osono, M., et al. 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 J. Antibiot. (Tokyo) 47(5),536-540(1994).
2. Masuda, T., Watanabe, S.-i., Amemiya, M., et al. Inhibitory effect of cytostatin on spontaneous lung metastases of B16-BL6 melanoma cells J. Antibiot. (Tokyo) 48(6),528-529(1995).
3. Yamazaki, K., Amemiya, M., Ishizuka, M., et al. Screening for apoptosis inducers in microbial products and induction of apoptosis by cytostatin J. Antibiot. (Tokyo) 48(10),1138-1140(1995).
4. Kawada, M., Amemiya, M., Ishizuka, M., et al. Cytostatin, an inhibitor of cell adhesion to extracellular matrix, selectively inhibits protein phosphatase 2A Biochim. Biophys. Acta 1452(2),209-217(1999).
5. Swingle, M.R., Amable, L., Lawhorn, B.G., et al. Structure-activity relationship studies of fostriecin, cytostatin, and key analogs, with PP1, PP2A, PP5, and (β12-β13)-chimeras (PP1/PP2A and PP5/PP2A), provide further insight into the inhibitory actions of fostriecin family inhibitors J. Pharmacol. Exp. Ther. 331(1),45-53(2009). |
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