Disintegrin-like Protein Strategy to Inhibit Aggressive Triple-Negative Breast Cancer

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom of Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets & alpha;5 & beta;1, & alpha;v & beta;3, and & alpha;v & beta;6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of human umbilical vein endothelial cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast-growth-factor-2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 & mu;M of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50% reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 & mu;M of Leb-C. Collectively, these findings suggest the potential utility of this disintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.

Automated summary

This study demonstrated that Leb-C derived from the venom of Macrovipera lebetina transmediterrannea snakes disrupted the adhesion, migration, and invasion capabilities of breast cancer cells, as well as the adhesion, migration, and invasion of endothelial cells and fibroblast-growth-factor-2-induced proliferation of endothelial cells. In vivo experiments using nude mice showed that treatment with Leb-C resulted in a significant reduction in xenograft tumor size and tumor angiogenesis. These findings suggest the potential utility of Leb-C for inhibiting aggressive and resistant metastatic breast cancer.