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

Inès Limam; Mohamed Abdelkarim; Mohamed El Ayeb; Michel Crepin; Naziha Marrakchi; Mélanie Di Benedetto

doi:10.20944/preprints202306.0808.v2

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preprints.org > medicine and pharmacology > oncology and oncogenics > doi: 10.20944/preprints202306.0808.v2

Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

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

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)

A peer-reviewed article of this Preprint also exists.

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 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 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.

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Comments (1)

Comment 1

Received: 13 June 2023
Commenter: Inès Limam
Commenter's Conflict of Interests: Author

Comment: Dear Editor,
In the revised version, I only changed the corresponding author who becomes Dr Mélanie Di Benedetto instead of Inès Limam.
Thank you for your understanding.
Kind regards,
Inès Limam

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