PIVL, a new serine protease inhibitor from Macrovipera lebetina transmediterranea venom, impairs motility of human glioblastoma cells

Morjen, Maram; Kallech-Ziri, Olfa; Bazaa, Amine; Othman, Houcemeddine; Kamel, Mabrouk; Zouari-Kessentini, Raoudha; Sanz, Libia; Calvete, Juan J.; Srairi-Abid, Najet; Ayeb, Mohamed El; Luis, José; Marrakchi, Naziha

doi:10.1016/j.matbio.2012.11.015

Cited by 52 publications

(37 citation statements)

References 57 publications

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“…Snake venoms are a well-known natural source in drug development and discovery studies (Lewis & Garcia 2003;Koh et al 2006;Fox & Serrano 2007;Vyas et al 2013). Although there are published reports showing selected biological activities of crude venom or purified proteins of different subspecies of M. lebetina (Tõnismägi et al 2006;Son et al 2007;Bazaa et al 2009;Nalbantsoy et al 2012;Park et al 2012;Shebl et al 2012a;Morjen et al 2013), the combination of cancer cell lines and microorganisms included for screening in the present study has not been chosen in earlier studies, particularly on M. l. obtusa subspecies venom. The present study investigated cytotoxic effects on cancer and non-cancerous cells and the antimicrobial properties of Anatolian M. l. obtusa crude venom in order to assess its potential for further bioactivity-guided characterization studies.…”

Section: Discussionmentioning

confidence: 98%

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

Özen

İğci

Yalçın

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: Discussionmentioning

confidence: 98%

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

Özen

İğci

Yalçın

et al. 2015

Frontiers in Life Science

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“…Structurally, VaaChi belongs to the non-neurotoxic snake venom KPIs that have lost the ability to inhibit conductance of K + and Ca 2+ channels [74]. Its amino acid sequence is 87% identical to that of Macrovipera lebetina transmediterranea venom KPI which is able to inhibit adhesion, migration and invasion of human glioblastoma U87 cells by binding to integrin receptors via the RGN motif [75]. The RGN motif is also present in VaaChi and, probably, also in Vbb KPI, suggesting a cancer inhibiting activity.…”

Section: Kunitz-type Protease Inhibitors (Kpis)mentioning

confidence: 99%

Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications

Latinović

Leonardi

Šribar

et al. 2016

Journal of Proteomics

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“…Other snake venom Kunitz-type peptidase inhibitors have been demonstrated to specifically inhibit the proteolytic activity of trypsin (Ritonja et al, 1983; Shafqat et al, 1990; Chou et al, 2010). A new Kunitz-type serine peptidase inhibitor named PIVL, isolated from the Tunisian viper Macrovipera lebetina transmediterranea venom was able to selectively inactivate trypsin but not chymotrypsin (Morjen et al, 2013). The intermolecular interactions of subsites resulting in the elongation on both sides of the scissile bond, which are very important for the mechanism of inhibition of serine peptidases by peptidase inhibitors, providing the base for the inhibitory specificity (Bode et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of tenerplasminin-1, a serine peptidase inhibitor with antiplasmin activity from the coral snake ( Micrurus tener tener ) venom

Vivas

Ibarra

Salazar

et al. 2016

Comparative Biochemistry and Physiology Part C: Toxicology &

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A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus tener tener (Mtt) venom. It showed a molecular mass of 6542 Da, similarly to Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin (0.5 nM) on synthetic substrate S-2251 was inhibited by 91% following the incubation with TP1 (1 nM). Aprotinin (2 nM) used as the positive control of inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic activity (0.05 nM) was inhibited by 67% following incubation with TP1 (0.1 nM). The degradation of fibrinogen chains induced by plasmin, trypsin or elastase was inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains, previously attributed to metallopeptidases, was not abolished by TP1. The tPA-clot lysis assay showed that TP1 (0.2 nM) acts like aprotinin (0.4 nM) inducing a delay in lysis time and lysis rate which may be associated with the inhibition of plasmin generated from the endogenous plasminogen activation. TP1 is the first serine protease plasmin-like inhibitor isolated from Mtt snake venom which has been characterized in relation to its mechanism of action, formation of a plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a biological characteristic of great interest in the field of biomedical research. They could be used to regulate the fibrinolytic system in pathologies such as metastatic cancer, parasitic infections, hemophilia and other hemorrhagic syndromes, in which an intense fibrinolytic activity is observed.

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PIVL, a new serine protease inhibitor from Macrovipera lebetina transmediterranea venom, impairs motility of human glioblastoma cells

Cited by 52 publications

References 57 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

Venomics of Vipera berus berus to explain differences in pathology elicited by Vipera ammodytes ammodytes envenomation: Therapeutic implications

Purification and characterization of tenerplasminin-1, a serine peptidase inhibitor with antiplasmin activity from the coral snake ( Micrurus tener tener ) venom

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