Leucurogin and melanoma therapy

Almeida, M. Conceição; Santos, Ivan Carlos dos; Paschoalin, Thaysa; Travassos, Luiz R.; Mauch, Cornelia; Zigrino, Paola; Pesquero, João Bosco; Pesquero, Jorge L.; Higuchi, Debora Ayame

doi:10.1016/j.toxicon.2018.12.005

Cited by 6 publications

(3 citation statements)

References 70 publications

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“…Furthermore, several reports on disintegrin-like proteins have highlighted their capacity to interfere with endothelial cell functions. For instance, leucurogin, a D/C protein cloned from Bothrops leucurus venom, inhibited HUVEC tube formation at 4.8 µM after an 18 h incubation period [51]. Another study demonstrated that 1 µM of alternagin-C, an isolated disintegrin-like protein from Bothrops alternatus venom, reduced various VEGFinduced angiogenic events in HUVEC, including adhesion (by 63%), viability (by 27%), migration (by 55%), and tube formation (by 53%) time [52].…”

Section: Discussionmentioning

confidence: 99%

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

Limam,

Abdelkarim,

El Ayeb

et al. 2023

IJMS

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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 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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Section: Discussionmentioning

confidence: 99%

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

Limam,

Abdelkarim,

El Ayeb

et al. 2023

IJMS

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“…This toxin prevented growth, migration, proliferation and vascular structure formation in human melanoma BLM and murine melaonoma B16F10 Next-2 cells by inhibiting integrin-collagen binding (Almeida et al, 2019).…”

Section: Snake Venom Dis Anticancer Activitiesmentioning

confidence: 99%

“…Furthermore, leucurogin prevented angiogenesis and vascularisation process in a sponge implant model after 7 days in a dose‐dependent manner when compared with the control group injected with 100 μl 0.9% saline daily. This toxin prevented growth, migration, proliferation and vascular structure formation in human melanoma BLM and murine melaonoma B16F10 Next‐2 cells by inhibiting integrin‐collagen binding (Almeida et al, 2019).…”

Section: Anticancer Effects Of Individual Snake Venom Toxinsmentioning

confidence: 99%

Snake venom toxins: Potential anticancer therapeutics

Offor,

Piater

2023

J of Applied Toxicology

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Snake venom contains a cocktail of compounds dominated by proteins and peptides, which make up the toxin. The toxin components of snake venom attack several targets in the human body including the neuromuscular system, kidney and blood coagulation system and cause pathologies. As such, the venom toxins can be managed and used for the treatment of these diseases. In this regard, Captopril used in the treatment of cardiovascular diseases was the first animal venom toxin‐based drug approved by the US Food and Drug Administration and the European Medicines Agency. Cancers cause morbidity and mortality worldwide. Due to side effects associated with the current cancer treatments including chemotherapy, radiotherapy, immunotherapy, hormonal therapy and surgery, there is a need to improve the efficacy of current treatments and/or develop novel drugs from natural sources including animal toxin‐based drugs. There is a long history of earlier and ongoing studies implicating snake venom toxins as potential anticancer therapies. Here, we review the role of crude snake venoms and toxins including phospholipase A2, L‐amino acid oxidase, C‐type lectin and disintegrin as potential anticancer agents tested in cancer cell lines and animal tumour models in comparison to normal cell lines. Some of the anti‐tumour activities of snake venom toxins include induction of cytotoxicity, apoptosis, cell cycle arrest and inhibition of metastasis, angiogenesis and tumour growth. We thus propose the advancement of multidisciplinary approaches to more pre‐clinical and clinical studies for enhanced bioavailability and targeted delivery of snake venom toxin‐based anticancer drugs.

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