A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition

Aranda-Souza, Mary Ângela; Rossato, Franco Aparecido; Costa, Rute Alves Pereira e; Figueira, Tiago Rezende; Castilho, Roger F.; Guarniere, Miriam C.; Nunes, Erika S.; Coelho, Luana Cassandra Breitenbach Barroso; Correia, Maria T.S.; Vercesi, Anı́bal E.

doi:10.1016/j.toxicon.2014.02.018

Cited by 37 publications

(15 citation statements)

References 31 publications

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“…The result of this assay showed the reduction of MTT to absolute values of 0.03 and 0.07 of BJ and BE, respectively, thus confirming the cytotoxicity of these venoms in SiHa and HeLa cell lines. According to Aranda-Souza et al [30], a reduction was also observed of melanoma cells (B16-F10) when treated with a lectin extracted BIL in B. leucurus snake venom. When Nunes et al [31] used BIL venom of the same species B. leucurus in K562 cells (erythromyeloblastoid human leukemia cell line), it showed the cytotoxic activity, while HaCaT cells (normal cell) were not affected.…”

Section: Discussionmentioning

confidence: 91%

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Bernardes-Oliveira

Gomes

Palomino

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Bothrops jararaca (BJ) and Bothrops erythromelas (BE) are viper snakes found in South-Southeast and Northeast regions of Brazil, respectively. Snake venoms are bioactive neurotoxic substances synthesized and stored by venom glands, with different physiological and pharmacological effects, recently suggesting a possible preference for targets in cancer cells; however, mechanisms of snakes have been little studied. Here, we investigated the mechanism responsible for snake crude venoms toxicity in cultured cervical cancer cells SiHa and HeLa. We show that BJ and BE snake crude venoms exert cytotoxic effects to these cells. The percentage of apoptotic cells and cell cycle analysis and cell proliferation were assessed by flow cytometry and MTT assay. Detection of mitochondrial membrane potential (Rhodamine-123), nuclei morphological change, and DNA fragmentation were examined by staining with DAPI. The results showed that both the BJ and BE venoms were capable of inhibiting tumor cell proliferation, promoting cytotoxicity and death by apoptosis of target SiHa and HeLa cells when treated with BJ and BE venoms. Furthermore, data revealed that both BJ venoms in SiHa cell promoted nuclear condensation, fragmentation, and formation of apoptotic bodies by DAPI assay, mitochondrial damage by Rhodamine-123, and cell cycle block in the G1-G0 phase. BJ and BE venoms present anticancer potential, suggesting that both Bothrops venoms could be used as prototypes for the development of new therapies.

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Section: Discussionmentioning

confidence: 91%

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Bernardes-Oliveira

Gomes

Palomino

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…Plant seed lectin changes mitochondrial membranes leading to increased cytoplasmic calcium concentration and consequent reactive oxygen production, which induces necrotic cell death (Irigoin et al, 2009; Fernandes et al, 2010; Aranda-Souza et al, 2014). Even crude extract, the most unpurified fraction of latex, did not cause cytotoxicity in both cells, indicating that other components present did not damage these cells.…”

Section: Resultsmentioning

confidence: 99%

Eutirucallin: A Lectin with Antitumor and Antimicrobial Properties

Palharini

Richter

Silva

et al. 2017

Front. Cell. Infect. Microbiol.

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Eutirucallin is a lectin isolated from the latex of Euphorbia tirucalli, a plant known for its medical properties. The present study explores various characteristics of Eutirucallin including stability, cytotoxicity against tumor cells, antimicrobial and antiparasitic activities. Eutirucallin was stable from 2 to 40 days at 4°C, maintained hemagglutinating activity within a restricted range, and showed optimal activity at pH 7.0–8.0. Eutirucallin presented antiproliferative activity for HeLa, PC3, MDA-MB-231, and MCF-7 tumor cells but was not cytotoxic for non-tumorigenic cells such as macrophages and fibroblasts. Eutirucallin inhibited the Ehrlich ascites carcinoma in vivo and it was also observed that Eutirucallin inhibited 62.5% of Escherichia coli growth. Also, Eutirucallin showed to be effective when tested directly against Toxoplasma gondii infection in vitro. Therefore, this study sheds perspectives for pharmacological applications of Eutirucallin.

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“…This hypothesis will be tested in the future by checking HIF-1α expression in the control and treated group. Accumulated evidence shows that several isolated or recombinant snake venom toxins exhibit anti-cancer effects in vitro and in vivo preclinical models, triggering cell death via the mitochondrial intrinsic apoptotic pathway or necrosis [1,11,32]. Our results revealed that obtustatin did not induce any signs of apoptotic death in the treatment of animals with sarcoma.…”

Section: Discussionmentioning

confidence: 53%

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

et al. 2019

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Obtustatin, isolated from the Levantine Viper snake venom (Macrovipera lebetina obtusa-MLO), is the shortest known monomeric disintegrin shown to specifically inhibit the binding of the α1β1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through α1β1 integrin inhibition in endothelial cells. To explore the therapeutic potential of obtustatin, we studied its effect in S-180 sarcoma-bearing mice model in vivo as well as in human dermal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick embryo chorioallantoic membrane assay (CAM assay). Our in vivo results show that obtustatin inhibits tumour growth by 33%. The expression of vascular endothelial growth factor (VEGF) increased after treatment with obtustatin, but the level of expression of caspase 8 did not change. In addition, our results demonstrate that obtustatin inhibits FGF2-induced angiogenesis in the CAM assay. Our in vitro results show that obtustatin does not exhibit cytotoxic activity in HMVEC-D cells in comparison to in vivo results. Thus, our findings disclose that obtustatin might be a potential candidate for the treatment of sarcoma in vivo with low toxicity.

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A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition

Cited by 37 publications

References 31 publications

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

Eutirucallin: A Lectin with Antitumor and Antimicrobial Properties

The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

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