Tumor cytotoxicity of leucurolysin-B, a P-III snake venom metalloproteinase from Bothrops leucurus

Gabriel, LM; Sanchez, EF; Silva, SG; Santos, RG

doi:10.1590/s1678-91992012000100004

Cited by 19 publications

(6 citation statements)

References 24 publications

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“…A number of anticancer drugs exert their effects by inducing apoptosis [17]. Cytotoxic compounds that disrupt DNA and chromosomal integrity leading to apoptotic death evoke DNA condensation and fragmentation that can be visualized as very small focal bright points when stained by DAPI [18]. Analysis of chromosomal alterations were made using 4',6-diamidine-2'-phenindole dihydrocloride (DAPI) [19] (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

ROS-Mediated Cytotoxic Effect of Copper(II) Hydrazone Complexes against Human Glioma Cells

et al. 2014

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2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

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Section: Resultsmentioning

confidence: 99%

ROS-Mediated Cytotoxic Effect of Copper(II) Hydrazone Complexes against Human Glioma Cells

et al. 2014

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“…Integrins activate intracellular signaling controlling cytoskeleton organization, cell polarity, leading-edge formation, and mitochondrial bioenergetics of migrating cancer cells [ 22 , 99 , 100 ]; therefore, disrupting the ECM–integrin–metabolism axis is an attractive anti-cancer target for new antagonist molecules based on SVMP scaffolds. Accordingly, some SVMPs P-III inhibit proliferation [ 101 ] and induce apoptosis [ 102 , 103 ] in cancer cells. Interestingly, our results indicate that the triple-negative breast cancer (TNBC) cell line MDA-MB-231, which exhibits high metabolic plasticity for supporting migration [ 45 , 104 ], was more sensitive to the Pic-III treatment, reducing ATP levels and mitochondrial respiration compared to breast fibroblast RMF-621.…”

Section: Discussionmentioning

confidence: 99%

Pictolysin-III, a Hemorrhagic Type-III Metalloproteinase Isolated from Bothrops pictus (Serpentes: Viperidae) Venom, Reduces Mitochondrial Respiration and Induces Cytokine Secretion in Epithelial and Stromal Cell Lines

Toledo

Alvarenga

2023

Pharmaceutics

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From the venom of the Bothrops pictus snake, an endemic species from Peru, we recently have described toxins that inhibited platelet aggregation and cancer cell migration. In this work, we characterize a novel P-III class snake venom metalloproteinase, called pictolysin-III (Pic-III). It is a 62 kDa proteinase that hydrolyzes dimethyl casein, azocasein, gelatin, fibrinogen, and fibrin. The cations Mg2+ and Ca2+ enhanced its enzymatic activity, whereas Zn2+ inhibited it. In addition, EDTA and marimastat were also effective inhibitors. The amino acid sequence deduced from cDNA shows a multidomain structure that includes a proprotein, metalloproteinase, disintegrin-like, and cysteine-rich domains. Additionally, Pic-III reduces the convulxin- and thrombin-stimulated platelet aggregation and in vivo, it has hemorrhagic activity (DHM = 0.3 µg). In epithelial cell lines (MDA-MB-231 and Caco-2) and RMF-621 fibroblast, it triggers morphological changes that are accompanied by a decrease in mitochondrial respiration, glycolysis, and ATP levels, and an increase in NAD(P)H, mitochondrial ROS, and cytokine secretion. Moreover, Pic-III sensitizes to the cytotoxic BH3 mimetic drug ABT-199 (Venetoclax) in MDA-MB-231 cells. To our knowledge, Pic-III is the first SVMP reported with action on mitochondrial bioenergetics and may offer novel opportunities for promising lead compounds that inhibit platelet aggregation or ECM–cancer-cell interactions.

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“…Leucurolysin‐B (Leuc‐B), a P‐III metalloproteinase from B. leucurus venom, showed cytotoxicity and nuclear condensation effect on T98, U87 and RT2, MCF‐7, EAC and UACC cancer cell lines (Gabriel et al, 2012). Leuc‐B possesses a disintegrin‐like ECD sequence in comparison to the typical RGD motif and a cysteine‐rich C‐terminal domain.…”

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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Tumor cytotoxicity of leucurolysin-B, a P-III snake venom metalloproteinase from Bothrops leucurus

Cited by 19 publications

References 24 publications

ROS-Mediated Cytotoxic Effect of Copper(II) Hydrazone Complexes against Human Glioma Cells

ROS-Mediated Cytotoxic Effect of Copper(II) Hydrazone Complexes against Human Glioma Cells

Pictolysin-III, a Hemorrhagic Type-III Metalloproteinase Isolated from Bothrops pictus (Serpentes: Viperidae) Venom, Reduces Mitochondrial Respiration and Induces Cytokine Secretion in Epithelial and Stromal Cell Lines

Snake venom toxins: Potential anticancer therapeutics

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