article · International Journal of Molecular Sciences
Research investigated the potential of Leb-C, a disintegrin-like protein from snake venom, to inhibit aggressive triple-negative breast cancer. Previous work showed Leb-C targets specific integrins, and this study found it disrupted the adhesion, migration, and invasion of MDA-MB-231 breast cancer cells and their highly metastatic sub-population. Leb-C also significantly suppressed the adhesion, migration, invasion, and proliferation of human umbilical vein endothelial cells. In experiments using nude mice, Leb-C treatment led to a substantial 73% reduction in tumour size and a 50% reduction in tumour angiogenesis in xenografts. These findings suggest Leb-C could be useful for treating aggressive and resistant metastatic breast cancer.
Aggressive and metastatic breast cancer, particularly triple-negative, remains challenging to treat. This research explores a novel approach using a snake venom-derived protein, offering a potential new therapeutic strategy to combat tumour growth and spread, which could improve patient outcomes.
This research indicates a potential therapeutic strategy for aggressive and resistant metastatic breast cancer. Leb-C could be developed as a drug candidate to inhibit tumour growth and angiogenesis. This is early-stage research, with in vivo testing in mice, suggesting a pathway towards pharmaceutical development for oncology applications.
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snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3, and αvβ6 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 µM 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 µM of Leb-C. Collectively, these findings suggest the potential utility of this disintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.
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DOI: 10.3390/ijms241512219
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