Alternagin-C, an alpha2beta1 integrin ligand, attenuates collagen-based adhesion, stimulating the metastasis suppressor 1 expression in triple-negative breast tumor cells

Moritz, Milene Nóbrega de Oliveira; Casali, Bruna C.; Stotzer, Uliana Sbeguen; Santos, Patty Karina dos; Selistre-de-Araújo, Heloísa Sobreiro

doi:10.1016/j.toxicon.2022.02.001

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…To our knowledge, only one study has reported on the effects of the disintegrin-like protein family in breast carcinoma. Alternagin-C, an ECD-disintegrin-like protein, was identified as a potent antagonist of α2β1 integrin, capable of attenuating the adhesion of MDA-MB-231 cells to collagen I but not inhibiting cell migration [44]. However, there are limited studies describing the anti-tumor effects of the disintegrin-like protein family.…”

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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“…Alternagin-C, an ECD-disintegrin-like protein from Bothrops alternatus snake venom, inhibits the binding of α 2 β 1 integrins and impairs angiogenesis in HUVEC (dos Santos et al, 2020). Additionally, alternagin-C has been shown to stimulate the expression of metastasis suppressor 1 in breast tumour cells (Moritz et al, 2022).…”

Section: Snake Venom Dis Anticancer Activitiesmentioning

confidence: 99%

“…Alternagin‐C, an ECD‐disintegrin‐like protein from Bothrops alternatus snake venom, inhibits the binding of α 2 β 1 integrins and impairs angiogenesis in HUVEC (dos Santos et al, 2020). Additionally, alternagin‐C has been shown to stimulate the expression of metastasis suppressor 1 in breast tumour cells (Moritz et al, 2022). Recombinant rubistatin (r‐Rub), an MVD disintegrin cloned from a Crotalus ruber ruber venom gland inhibited cell migration and proliferation, and induced apoptosis in SK‐Mel‐28 cell line but not in T24 or HeLa cells (Carey et al, 2012).…”

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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“…After binding to collagen, integrin α2β1 was shown to activate the pro-oncogenic YAP in hepatoma cells, which correlated well with tumor progression and outcome in patients [ 83 ]. Alternagin-C is a substance that binds to integrin α2β1 and can weaken the adhesion of triple-negative breast cancer cells to collagen matrix while stimulating the expression of transfer inhibitory factor 1 [ 84 ]. It has been revealed that integrin α2β1 is involved in protecting tumor cells from aging, and reducing the expression of integrin α2β1 triggers an atypical signaling mechanism based on AKT, resulting in the process of cellular aging [ 85 ].…”

Section: Function Of the Integrin β1 Familymentioning

confidence: 99%

The characteristics and the multiple functions of integrin β1 in human cancers

Sun,

Guo,

Xie

et al. 2023

J Transl Med

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Integrins, which consist of two non-covalently linked α and β subunits, play a crucial role in cell–cell adhesion and cell-extracellular matrix (ECM) interactions. Among them, integrin β1 is the most common subunit and has emerged as a key mediator in cancer, influencing various aspects of cancer progression, including cell motility, adhesion, migration, proliferation, differentiation and chemotherapy resistance. However, given the complexity and sometimes contradictory characteristics, targeting integrin β1 for therapeutics has been a challenge. The emerging understanding of the mechanisms regulating by integrin β1 may guide the development of new strategies for anti-cancer therapy. In this review, we summarize the multiple functions of integrin β1 and signaling pathways which underlie the involvement of integrin β1 in several malignant cancers. Our review suggests the possibility of using integrin β1 as a therapeutic target and highlights the need for patient stratification based on expression of different integrin receptors in future clinical studies.

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Alternagin-C, an alpha2beta1 integrin ligand, attenuates collagen-based adhesion, stimulating the metastasis suppressor 1 expression in triple-negative breast tumor cells

Cited by 8 publications

References 51 publications

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

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

Snake venom toxins: Potential anticancer therapeutics

The characteristics and the multiple functions of integrin β1 in human cancers

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