Version 1
: Received: 12 June 2023 / Approved: 12 June 2023 / Online: 12 June 2023 (09:36:03 CEST)
Version 2
: Received: 12 June 2023 / Approved: 13 June 2023 / Online: 13 June 2023 (04:03:08 CEST)
Limam, I.; Abdelkarim, M.; El Ayeb, M.; Crepin, M.; Marrakchi, N.; Di Benedetto, M. Disintegrin-like Protein Strategy to Inhibit Aggressive Triple-Negative Breast Cancer. Int. J. Mol. Sci.2023, 24, 12219.
Limam, I.; Abdelkarim, M.; El Ayeb, M.; Crepin, M.; Marrakchi, N.; Di Benedetto, M. Disintegrin-like Protein Strategy to Inhibit Aggressive Triple-Negative Breast Cancer. Int. J. Mol. Sci. 2023, 24, 12219.
Limam, I.; Abdelkarim, M.; El Ayeb, M.; Crepin, M.; Marrakchi, N.; Di Benedetto, M. Disintegrin-like Protein Strategy to Inhibit Aggressive Triple-Negative Breast Cancer. Int. J. Mol. Sci.2023, 24, 12219.
Limam, I.; Abdelkarim, M.; El Ayeb, M.; Crepin, M.; Marrakchi, N.; Di Benedetto, M. Disintegrin-like Protein Strategy to Inhibit Aggressive Triple-Negative Breast Cancer. Int. J. Mol. Sci. 2023, 24, 12219.
Abstract
Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3 and αv6 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 dinsintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.
Keywords
Disintegrin-like; breast cancer; TNBC; HUVEC; migration; angiogenesis
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.