CAST inhibition of MMP activity

Sensitizing tumor cells to chemotherapeutic agents is not the only mode of action of CAST. This multipotent product also has the potential to help prevent cancer dissemination by antagonizing the action of some metalloproteinases, as shown in an in vitro assay for MMP-2 activity. The inhibitory effect of CAST towards the gelatinolytic activity of MMP-2 was confirmed using a fluorescence-based in vitro assay (Fig. 4). In this assay, a purified MMP-2 enzyme is incubated in the presence of a fluorogenic substrate with and without CAST. The MMP-2 activity can be measured through the reading of the emitted fluorescence. This experiment demonstrated that CAST inhibited MMP-2 activity by 90%. Figure 6: Inhibitory action of CAST on MMP-2 activity

Figure 4: Inhibitory action of CAST on MMP-2 activity

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which can degrade the major components of the extracellular matrix (ECM). Cancer cells subvert MMPs activity to promote invasion of the surrounding tissues as well as metastasis to distant ones (Fig. 5). MMPs, by releasing growth factors sequestered in the extracellular matrix, also are thought to promote the growth of these tumor cells once they have metastasized. Thus by opposing MMP-2 activity, CAST shall prevent tumor progression and metastatis.