A novel metalloprotease from Vipera lebetina venom induces human endothelial cell apoptosis

Trummal, Katrin; Tõnismägi, Külli; Siigur, Ene; Aaspõllu, Anu; Lopp, Annika; Sillat, Tarvo; Saat, Riste; Kasak, Lagle; Tammiste, Indrek; Kogerman, Priit; Kalkkinen, Nisse; Siigur, Jiiri

doi:10.1016/j.toxicon.2005.03.008

Cited by 72 publications

(40 citation statements)

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“…These include necrosis, induction of apoptosis, overregulation or downregulation of cell cycle proteins and deterioration of cell membrane integrity. Apoptosis-inducing cytotoxic activities of crude venoms or purified proteins such as metalloproteinases and LAAO from different subspecies of M. lebetina have been reported on various cancer and non-cancerous cells (Trummal et al 2005;Son et al 2007;Park et al 2009Park et al , 2012Shebl et al 2012a;Samel et al 2012Samel et al , 2013. Induction of apoptosis may be one of the mechanisms responsible for the cytotoxic effect of Anatolian M. l. obtusa venom observed in the present study.…”

Section: Discussionsupporting

confidence: 63%

Screening of cytotoxic and antimicrobial activity potential of AnatolianMacrovipera lebetina obtusa(Ophidia: Viperidae) crude venom

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et al. 2015

Frontiers in Life Science

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The effects of snake venoms have been well known since ancient times. They contain a variety of biologically active proteins which have therapeutic potential. This study investigated the cytotoxic and antimicrobial activities of Anatolian Macrovipera lebetina obtusa venom against various cancer cells, Gram-negative and Gram-positive bacteria, and a fungal species. A549, HeLa, CaCo-2, U-87 MG and MCF-7 cancer cell lines and a normal cell line (Vero) were screened by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The antimicrobial activity was evaluated by determining the minimum inhibitory concentration (MIC) using the broth dilution method. The species included were Escherichia coli ATCC 25922, E. coli 0157:H7, Enterococcus faecalis, Enterococcus faecium DSM 13590, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Salmonella typhimurium CCM 5445, Proteus vulgaris ATCC 6957, Bacillus cereus ATCC 7064 and Candida albicans ATCC 10239. Half-maximal inhibitory concentration (IC 50 ) values of M. l. obtusa venom on cultured cells varied from 1.18 ± 0.11 to 12.80 ± 0.22 μg/ml, with the most potent activities against Vero, U-87 MG, MCF-7 and CaCo-2 cells. Venom showed moderate antifungal activity against C. albicans, with an MIC of 62.50 μg/ml. In short, the venom of Anatolian M. l. obtusa showed promising results as a potential source of alternative therapeutics, cytotoxic and antifungal agent prototypes.

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Section: Discussionsupporting

confidence: 63%

Screening of cytotoxic and antimicrobial activity potential of AnatolianMacrovipera lebetina obtusa(Ophidia: Viperidae) crude venom

Özen

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et al. 2015

Frontiers in Life Science

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“…Furthermore, venoms or purified proteins from different subspecies of M. lebetina also induced apoptosis in other various cancers and non-cancerous cells, through different mechanisms. 18,20,21,44 Sanz et al 45 identified PLA2, LAAO, metalloproteinase, serine proteinase, natriuretic peptide, disintegrin, BPP and CRISP protein families in the venom of M. l. obtusa from Armenia by mass spectrometry-based proteomics approach. Igci and Demiralp 8 reported the similar protein content with additions of NGF, VEGF and protease inhibitor for Anatolian M. l. obtusa.…”

Section: 3639mentioning

confidence: 99%

In Vitro Cytotoxic and Proapoptotic Activities of Anatolian Macrovipera Lebetina Obtusa (Dwigubski, 1832) Crude Venom on Cultured K562 Human Chronic Myelogenous Leukemia Cells.

Süzergöz¹

2016

UHOD

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In the context of searching for anticancer compounds in natural products, snake venom is one of the important sources for peptide/ protein based bioactive molecules. Proteins and peptides with anticancer activity were purified and identified from snake venoms. The aim of the present study was to determine the in vitro cytotoxicity of Macrovipera lebetina obtusa (Blunt-Nosed Viper) crude venom from southeastern Anatolia against K562 human chronic myelogenous leukemia (CML) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Adenosine tripohsphate (ATP) assays. Additionally, the apoptosis induction was assessed by morphological evaluation and immunohistochemical analysis for activated caspase-3. For histopahtological evaluation, haematoxylineosin, giemsa and papanicolau stains were used in combination. M. l. obtusa venom showed dose-dependent toxicity against K562 cells after 72 h treatment with different concentrations of crude venom. IC50 values were 0.45 and 0.37 µg/mL for MTT and ATP assays, respectively. Nuclear fragmentation and condensation, apoptotic bodies and activation of caspase-3, as an induction of apoptosis were also observed in K562 cells. Since apoptosis-inducing compounds are important for the treatment of cancer, further studies on Anatolian M. l. obtusa venom could result in the purification and identification of new proteins and peptides, which might have therapeutic value for the treatment of CML. Keywords: Anticancer, Apoptosis, Blunt-nosed viper, Macrovipera lebetina obtusa, Snake venom ÖZET Anadolu'da Yayılış Gösteren Macrovipera lebetina obtusa (Dwigubski, 1832) Zehrinin K562 İnsan Kronik Myeloid Lösemi Hücreleri Üzerinde in vitro Sitotoksik ve Apoptotik Aktiviteleri Doğal ürünlerde antikanser bileşiklerin araştırılması kapsamındaki çalışmalarda kullanılan önemli biyoaktif peptit/protein kaynaklarından biri de yılan zehridir. Yılan zehirlerinden antikanser etkili protein ve peptitler saflaştırılmış ve tanımlanmıştır. Bu çalışmanın amacı, güneydoğu Anadolu bölgesinde bulunan Macrovipera lebetina obtusa (Koca Engerek) ham zehrinin K562 insan kronik myeloid lösemi (KML) hücreleri üzerinde in vitro sitotokik etkisinin 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) ve Adenosine tripohsphate (ATP) testleri ile belirlenmesidir. Ek olarak, morfolojik değerlendirme ve aktif kaspaz-3 immünohistokimyasal analizi ile zehrin apoptotik etkisi de değerlendirilmiştir. Histopatolojik değerlendirme için hematoksilen-eozin, gimza ve papanikolau boyaları kullanılmıştır. M. l. obtusa zehrinin farklı konsantrasyonlarıyla 72 saatlik inkübasyon sonucunda K562 hücrelerine karşı doza bağlı toksisite görülmüştür. IC50 değerleri MTT ve ATP testleriyle sırasıyla 0.45 and 0.37 µg/mL olarak hesaplanmıştır. Ayrıca apoptoz uyarımının göstergeleri olarak nükleer fragmentasyon ve yoğunlaşma, apoptotik veziküller ve kaspaz-3 aktivasyonu gözlenmiştir. Apoptoza neden olan bileşiklerin kanser tedavisinde önemli bir yeri olması göz önünde bulundurulduğunda, Anadolu'da bulu...

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“…The metalloproteinases (SVMPs) and A-disintegrin proteinases (ADAMs) (Juárez et al, 2006;Moura-daSilva et al, 2011;Trummal et al, 2005) comprise the M12b subfamily of zinc-dependent reprolysins. Both enzymes, along with the non-enzyme C-type lectin-like proteins, are important snake venom components (Bode et al, 1993;Stokër et al, 1995;Bjarnason and Fox, 1995).…”

Section: Introductionmentioning

confidence: 99%

Characterization of a hemorrhage-inducing component present in Bitis arietans venom

Souza¹,

Magnoli²,

Silva³

2015

Afr. J. Biotechnol.

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Better characterization of individual snake venom toxins is useful for analyzing the association of their toxic domains and relevant antigenic epitopes. Here we analyzed the Bitis arietans hemorrhagicinducing toxin present in a representative venom sample. Among the 1´ to 5´ protein peaks isolated using a Sephacryl S 100 HR chromatography column, hemorrhagic activity was expressed by all according to the following intensity, P´5 > P´3 > P´2 >, P´4. The proteins were recognized and measured with antibodies present in polyvalent horse F(ab)´2 anti-B. arietans, Bitis spp., Lachesis muta, B. atrox, Bothrops spp., Crotalus spp., and Naja spp. or in IgY anti-B. arietans and anti-Bitis spp. using enzymelinked immunosorbent assays and western blotting. In addition, in an in vitro-in vivo assay these antivenoms were able to block hemorrhagic-inducing activity. The evident cross-reactivity expressed by different specific anti-venoms indicates that metalloproteinases induce an immunological signature indicating the presence of similar antigenic epitopes for several snake venoms.

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A novel metalloprotease from Vipera lebetina venom induces human endothelial cell apoptosis

Cited by 72 publications

References 43 publications

Screening of cytotoxic and antimicrobial activity potential of AnatolianMacrovipera lebetina obtusa(Ophidia: Viperidae) crude venom

Screening of cytotoxic and antimicrobial activity potential of AnatolianMacrovipera lebetina obtusa(Ophidia: Viperidae) crude venom

In Vitro Cytotoxic and Proapoptotic Activities of Anatolian Macrovipera Lebetina Obtusa (Dwigubski, 1832) Crude Venom on Cultured K562 Human Chronic Myelogenous Leukemia Cells.

Characterization of a hemorrhage-inducing component present in Bitis arietans venom

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