Toxins

Editorial

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2 pages, 193 KiB

Open AccessEditorial

Venom Toxins as Potential Targeted Therapies

by Hang Fai Kwok

Toxins 2019, 11(6), 338; https://doi.org/10.3390/toxins11060338 - 13 Jun 2019

Cited by 1 | Viewed by 2209

Abstract

Targeted therapy has been a very hot research topic in the last decade [...] Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

Research

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12 pages, 2782 KiB

Open AccessArticle

Bee Venom Alleviates Atopic Dermatitis Symptoms through the Upregulation of Decay-Accelerating Factor (DAF/CD55)

by Yenny Kim, Youn-Woo Lee, Hangeun Kim and Dae Kyun Chung

Toxins 2019, 11(5), 239; https://doi.org/10.3390/toxins11050239 - 26 Apr 2019

Cited by 15 | Viewed by 4490

Abstract

Bee venom (BV)—a complex mixture of peptides and toxic proteins including phospholipase A2 and melittin—promotes blood clotting. In this study, we investigated the anti-atopic properties of BV and the mechanism associated with its regulation of the complement system. BV treatment upregulated the mRNA [...] Read more.

Bee venom (BV)—a complex mixture of peptides and toxic proteins including phospholipase A2 and melittin—promotes blood clotting. In this study, we investigated the anti-atopic properties of BV and the mechanism associated with its regulation of the complement system. BV treatment upregulated the mRNA and protein levels of CD55 in THP-1 cells. Further experiments revealed that the phosphorylation of ERK was associated with upregulation of CD55. A complement-dependent cytotoxicity assay and a bacteria-killing assay showed that BV inactivated the complement system through the induction of CD55. The serum levels of C3 convertase (C3C) and Membrane attack complex (MAC) increased, while CD55 decreased in mice with AD-like lesions from DNCB treatment. However, the levels were inverted when the AD-like mice were treated with BV using subcutaneous injection, and we observed that the AD symptoms were alleviated. BV is often used to treat AD but its mechanism has not been elucidated. Here, we suggest that BV alleviates AD through the inactivation of the complement system, especially by the induction of CD55. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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12 pages, 3096 KiB

Open AccessArticle

A Hylarana latouchii Skin Secretion-Derived Novel Bombesin-Related Pentadecapeptide (Ranatensin-HLa) Evoke Myotropic Effects on the in vitro Rat Smooth Muscles

by Yan Lin, Nan Hu, Haoyang He, Chengbang Ma, Mei Zhou, Lei Wang and Tianbao Chen

Toxins 2019, 11(4), 204; https://doi.org/10.3390/toxins11040204 - 5 Apr 2019

Cited by 4 | Viewed by 3378

Abstract

Amphibians have developed successful defensive strategies for combating predators and invasive microorganisms encountered in their broad range of environments, which involve secretion of complex cocktails of noxious, toxic and diverse bioactive molecules from the skins. In recent years, amphibian skin secretions have been [...] Read more.

Amphibians have developed successful defensive strategies for combating predators and invasive microorganisms encountered in their broad range of environments, which involve secretion of complex cocktails of noxious, toxic and diverse bioactive molecules from the skins. In recent years, amphibian skin secretions have been considered as an extraordinary warehouse for the discovery of therapeutic medicines. In this study, through bioactivity screening of the Hylarana latouchii skin secretion-derived fractions, a novel peptide belonging to ranatensin subfamily (ranatensin-HLa) was discovered, and structurally and pharmacologically-characterised. It consists of 15 amino acid residues, pGlu-NGDRAPQWAVGHFM-NH₂, and its synthetic replicate was found to exhibit pharmacological activities on increasing the contraction of the in vitro rat bladder and uterus smooth muscles. Corresponding characteristic sigmoidal dose-response curves with EC₅₀ values of 7.1 nM and 5.5 nM were produced, respectively, in bladder and uterus. Moreover, the precursor of ranatensin-HLa showed a high degree of similarity to those of bombesin-like peptides from Odorrana grahami and Odorrana schmackeri. Hylarana latouchii skin continues to serve as a storehouse with diverse lead compounds for the development of therapeutically effective medicines. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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13 pages, 2169 KiB

Open AccessEditor’s ChoiceArticle

First Characterization of The Venom from Apis mellifera syriaca, A Honeybee from The Middle East Region

by Jacinthe Frangieh, Yahya Salma, Katia Haddad, Cesar Mattei, Christian Legros, Ziad Fajloun and Dany El Obeid

Toxins 2019, 11(4), 191; https://doi.org/10.3390/toxins11040191 - 30 Mar 2019

Cited by 46 | Viewed by 7598

Abstract

Bee venom is a mixture of several components with proven therapeutic benefits, among which are anti-inflammatory, analgesic, and various cardiovascular conditions. In this work, we analyzed for the first time the proteomic content and biological properties of the crude venom from Apis mellifera [...] Read more.

Bee venom is a mixture of several components with proven therapeutic benefits, among which are anti-inflammatory, analgesic, and various cardiovascular conditions. In this work, we analyzed for the first time the proteomic content and biological properties of the crude venom from Apis mellifera syriaca, a honeybee from the Middle East region. Using high-performance liquid chromatography-tandem mass spectrometry, we evidence the venom contains phospholipase A2, hyaluronidase, mast cell-degranulating peptide, adolapin, apamin, and melittin. The latter was purified by solid phase extraction method (SPE) and tested in parallel with crude venom for biological activities. Precisely, crude venom—but not melittin—exhibited antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa strains. Alongside, hemolytic activity was observed in human blood subjected to the venom at high doses. A. mellifera syriaca venom displayed antioxidant activities, and not surprisingly, PLA2 catalytic activity. Eventually, the venom proved to exert antiproliferative effects against MCF-7 and 3T3 cancer cells lines. This first report of a new bee venom opens new avenues for therapeutic uses of bee venoms. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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15 pages, 1745 KiB

Open AccessArticle

Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats

by Deman Najar, Börje Haraldsson, Annika Thorsell, Carina Sihlbom, Jenny Nyström and Kerstin Ebefors

Toxins 2018, 10(8), 333; https://doi.org/10.3390/toxins10080333 - 17 Aug 2018

Cited by 8 | Viewed by 7373

Abstract

Orellanine is a nephrotoxin found in mushrooms of the Cortinarius family. Accidental intake of this substance may cause renal failure. Orellanine is specific for proximal tubular cells and could, therefore, potentially be used as treatment for metastatic renal cancer, which originates from these [...] Read more.

Orellanine is a nephrotoxin found in mushrooms of the Cortinarius family. Accidental intake of this substance may cause renal failure. Orellanine is specific for proximal tubular cells and could, therefore, potentially be used as treatment for metastatic renal cancer, which originates from these cells. However, more information is needed about the distribution and elimination of orellanine from the body to understand its potential use for therapy. In this study, 5 mg/kg orellanine (unlabeled and ³H-labeled) was injected intravenously in rats (Wistar and Sprague Dawley). Distribution was measured (Wistar rats, n = 10, n = 12) using radioluminography and the highest amount of orellanine was found in the kidney cortex and bladder at all time-points investigated. The pharmacokinetic properties of orellanine was investigated using LC-MS/MS and β-scintillation to measure the amount of orellanine in plasma. Three groups of rats were investigated: control rats with intact kidneys (n = 10) and two groups with bilateral renal artery ligation (n = 7) where animals in one of these groups were treated with peritoneal dialysis (n = 8). Using LC-MS/MS, the half-life of orellanine was found to be 109 ± 6 min in the controls. In the groups with ligated renal arteries, orellanine had a half-life of 756 ± 98 min without and 238 ± 28 min with dialysis. Thus, orellanine was almost exclusively eliminated by glomerular filtration as well as by peritoneal dialysis. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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11 pages, 1522 KiB

Open AccessArticle

Biological Activities of Cationicity-Enhanced and Hydrophobicity-Optimized Analogues of an Antimicrobial Peptide, Dermaseptin-PS3, from the Skin Secretion of Phyllomedusa sauvagii

by Yining Tan, Xiaoling Chen, Chengbang Ma, Xinping Xi, Lei Wang, Mei Zhou, James F. Burrows, Hang Fai Kwok and Tianbao Chen

Toxins 2018, 10(8), 320; https://doi.org/10.3390/toxins10080320 - 7 Aug 2018

Cited by 21 | Viewed by 4408

Abstract

The skin secretions of the subfamily Phyllomedusinae have long been known to contain a number of compounds with antimicrobial potential. Herein, a biosynthetic dermaseptin-precursor cDNA was obtained from a Phyllomedusa sauvagii skin secretion-derived cDNA library, and thereafter, the presence of the mature peptide, [...] Read more.

The skin secretions of the subfamily Phyllomedusinae have long been known to contain a number of compounds with antimicrobial potential. Herein, a biosynthetic dermaseptin-precursor cDNA was obtained from a Phyllomedusa sauvagii skin secretion-derived cDNA library, and thereafter, the presence of the mature peptide, namely dermaseptin-PS3 (DPS3), was confirmed by LC–MS/MS. Moreover, this naturally occurring peptide was utilized to design two analogues, K^{5, 17}-DPS3 (introducing two lysine residues at positions 5 and 17 to replace acidic amino acids) and L^{10, 11}-DPS3 (replacing two neutral amino acids with the hydrophobic amino acid, leucine), improving its cationicity on the polar/unipolar face and hydrophobicity in a highly conserved sequence motif, respectively. The results in regard to the two analogues show that either increasing cationicity, or hydrophobicity, enhance the antimicrobial activity. Also, the latter analogue had an enhanced anticancer activity, with pretreatment of H157 cells with 1 µM L^{10, 11}-DPS3 decreasing viability by approximately 78%, even though this concentration of peptide exhibited no haemolytic effect. However, it must be noted that in comparison to the initial peptide, both analogues demonstrate higher membrane-rupturing capacity towards mammalian red blood cells. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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13 pages, 2762 KiB

Open AccessArticle

Burkholderia Lethal Factor 1, a Novel Anti-Cancer Toxin, Demonstrates Selective Cytotoxicity in MYCN-Amplified Neuroblastoma Cells

by Aleksander Rust, Sajid Shah, Guillaume M. Hautbergue and Bazbek Davletov

Toxins 2018, 10(7), 261; https://doi.org/10.3390/toxins10070261 - 27 Jun 2018

Cited by 10 | Viewed by 4725

Abstract

Immunotoxins are being investigated as anti-cancer therapies and consist of a cytotoxic enzyme fused to a cancer targeting antibody. All currently used toxins function via the inhibition of protein synthesis, making them highly potent in both healthy and transformed cells. This non-specific cell [...] Read more.

Immunotoxins are being investigated as anti-cancer therapies and consist of a cytotoxic enzyme fused to a cancer targeting antibody. All currently used toxins function via the inhibition of protein synthesis, making them highly potent in both healthy and transformed cells. This non-specific cell killing mechanism causes dose-limiting side effects that can severely limit the potential of immunotoxin therapy. In this study, the recently characterised bacterial toxin Burkholderia lethal factor 1 (BLF1) is investigated as a possible alternative payload for targeted toxin therapy in the treatment of neuroblastoma. BLF1 inhibits translation initiation by inactivation of eukaryotic initiation translation factor 4A (eIF4A), a putative anti-cancer target that has been shown to regulate a number of oncogenic proteins at the translational level. We show that cellular delivery of BLF1 selectively induces apoptosis in neuroblastoma cells that display MYCN amplification but has little effect on non-transformed cells. Future immunotoxins based on this enzyme may therefore have higher specificity towards MYCN-amplified cancer cells than more conventional ribosome-inactivating proteins, leading to an increased therapeutic window and decreased side effects. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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12 pages, 1557 KiB

Open AccessArticle

Domain II of Pseudomonas Exotoxin Is Critical for Efficacy of Bolus Doses in a Xenograft Model of Acute Lymphoblastic Leukemia

by Fabian Müller, Tyler Cunningham, Richard Beers, Tapan K. Bera, Alan S. Wayne and Ira Pastan

Toxins 2018, 10(5), 210; https://doi.org/10.3390/toxins10050210 - 21 May 2018

Cited by 8 | Viewed by 4200

Abstract

Moxetumomab pasudotox is a fusion protein of a CD22-targeting antibody and Pseudomonas exotoxin. Minutes of exposure to Moxetumomab achieves similar cell killing than hours of exposure to a novel deimmunized variant against some acute lymphoblastic leukemia (ALL). Because blood levels fall quickly, Moxetumomab [...] Read more.

Moxetumomab pasudotox is a fusion protein of a CD22-targeting antibody and Pseudomonas exotoxin. Minutes of exposure to Moxetumomab achieves similar cell killing than hours of exposure to a novel deimmunized variant against some acute lymphoblastic leukemia (ALL). Because blood levels fall quickly, Moxetumomab is more than 1000-fold more active than the deimmunized variant in vivo. We aimed to identify which part of Moxetumomab increases in vivo efficacy and generated five immunotoxins, tested time-dependent activity, and determined the efficacy in a KOPN-8 xenograft model. Full domain II shortened the time cells had to be exposed to die to only a few minutes for some ALL; deimmunized domain III consistently extended the time. Against KOPN-8, full domain II accelerated time to arrest protein synthesis by three-fold and tripled PARP-cleavage. In vivo efficacy was increased by more than 10-fold by domain II and increasing size, and therefore half-life enhanced efficacy two- to four-fold. In summary, in vivo efficacy is determined by the time cells have to be exposed to immunotoxin to die and serum half-life. Thus, domain II is most critical for activity against some ALL treated with bolus doses; however, immunotoxins lacking all but the furin-cleavage site of domain II may be advantageous when treating continuously. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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10 pages, 2868 KiB

Open AccessArticle

Bee Venom Phospholipase A2 Alleviate House Dust Mite-Induced Atopic Dermatitis-Like Skin Lesions by the CD206 Mannose Receptor

by Dasom Shin, Won Choi and Hyunsu Bae

Toxins 2018, 10(4), 146; https://doi.org/10.3390/toxins10040146 - 2 Apr 2018

Cited by 17 | Viewed by 5905

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic, erythematous, and eczematous skin plaques. We previously reported that phospholipase A2 (PLA2) derived from bee venom alleviates AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite extract ( [...] Read more.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic, erythematous, and eczematous skin plaques. We previously reported that phospholipase A2 (PLA2) derived from bee venom alleviates AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) and house dust mite extract (Dermatophagoides farinae extract, DFE) in a murine model. However, the underlying mechanisms of PLA2 action in actopic dermatitis remain unclear. In this study, we showed that PLA2 treatment inhibited epidermal thickness, serum immunoglobulin E (IgE) and cytokine levels, macrophage and mast cell infiltration in the ear of an AD model induced by DFE and DNCB. In contrast, these effects were abrogated in CD206 mannose receptor-deficient mice exposed to DFE and DNCB in the ear. These data suggest that bvPLA2 alleviates atopic skin inflammation via interaction with CD206. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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4064 KiB

Open AccessArticle

Anti-Helicobacter pylori Properties of the Ant-Venom Peptide Bicarinalin

by Jesus Guzman, Nathan Téné, Axel Touchard, Denis Castillo, Haouaria Belkhelfa, Laila Haddioui-Hbabi, Michel Treilhou and Michel Sauvain

Toxins 2018, 10(1), 21; https://doi.org/10.3390/toxins10010021 - 29 Dec 2017

Cited by 24 | Viewed by 7741

Abstract

The venom peptide bicarinalin, previously isolated from the ant Tetramorium bicarinatum, is an antimicrobial agent with a broad spectrum of activity. In this study, we investigate the potential of bicarinalin as a novel agent against Helicobacter pylori, which causes several gastric [...] Read more.

The venom peptide bicarinalin, previously isolated from the ant Tetramorium bicarinatum, is an antimicrobial agent with a broad spectrum of activity. In this study, we investigate the potential of bicarinalin as a novel agent against Helicobacter pylori, which causes several gastric diseases. First, the effects of synthetic bicarinalin have been tested against Helicobacter pylori: one ATCC strain, and forty-four isolated from stomach ulcer biopsies of Peruvian patients. Then the cytoxicity of bicarinalin on human gastric cells and murine peritoneal macrophages was measured using XTT and MTT assays, respectively. Finally, the preventive effect of bicarinalin was evaluated by scanning electron microscopy using an adherence assay of H. pylori on human gastric cells treated with bicarinalin. This peptide has a potent antibacterial activity at the same magnitude as four antibiotics currently used in therapies against H. pylori. Bicarinalin also inhibited adherence of H. pylori to gastric cells with an IC₅₀ of 0.12 μg·mL⁻¹ and had low toxicity for human cells. Scanning electron microscopy confirmed that bicarinalin can significantly decrease the density of H. pylori on gastric cells. We conclude that Bicarinalin is a promising compound for the development of a novel and effective anti-H. pylori agent for both curative and preventive use. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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3534 KiB

Open AccessArticle

Alternagin-C (ALT-C), a Disintegrin-Like Cys-Rich Protein Isolated from the Venom of the Snake Rhinocerophis alternatus, Stimulates Angiogenesis and Antioxidant Defenses in the Liver of Freshwater Fish, Hoplias malabaricus

by Diana Amaral Monteiro, Heloisa Sobreiro Selistre-de-Araújo, Driele Tavares, Marisa Narciso Fernandes, Ana Lúcia Kalinin and Francisco Tadeu Rantin

Toxins 2017, 9(10), 307; https://doi.org/10.3390/toxins9100307 - 28 Sep 2017

Cited by 4 | Viewed by 5109

Abstract

Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg⁻¹, via intra-arterial) on [...] Read more.

Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg⁻¹, via intra-arterial) on oxidative stress biomarkers, histological alterations, vascular endothelial growth factor (VEGF) production, and the degree of vascularization in the liver of the freshwater fish traíra, Hoplias malabaricus, seven days after the initiation of therapy. ALT-C treatment increased VEGF levels and hepatic angiogenesis. ALT-C also enhanced hepatic antioxidant enzymes activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, decreasing the basal oxidative damage to lipids and proteins in the fish liver. These results indicate that ALT-C improved hepatic tissue and may play a crucial role in tissue regeneration mechanisms. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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Review

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12 pages, 597 KiB

Open AccessReview

Malaysian Cobra Venom: A Potential Source of Anti-Cancer Therapeutic Agents

by Syafiq Asnawi Zainal Abidin, Yee Qian Lee, Iekhsan Othman and Rakesh Naidu

Toxins 2019, 11(2), 75; https://doi.org/10.3390/toxins11020075 - 1 Feb 2019

Cited by 19 | Viewed by 7915

Abstract

Cancer is a deadly disease and there is an urgent need for the development of effective and safe therapeutic agents to treat it. Snake venom is a complex mixture of bioactive proteins that represents an attractive source of novel and naturally-derived anticancer agents. [...] Read more.

Cancer is a deadly disease and there is an urgent need for the development of effective and safe therapeutic agents to treat it. Snake venom is a complex mixture of bioactive proteins that represents an attractive source of novel and naturally-derived anticancer agents. Malaysia is one of the world’s most biodiverse countries and is home to various venomous snake species, including cobras. Naja kaouthia, Naja sumatrana, and Ophiophagus hannah are three of the most common cobra species in Malaysia and are of medical importance. Over the past decades, snake venom has been identified as a potential source of therapeutic agents, including anti-cancer agents. This present review highlights the potential anticancer activity of the venom and purified venom protein of N. kaouthia, N. sumatrana, and O. hannah. In conclusion, this review highlights the important role of the venom from Malaysian cobras as an important resource that researchers can exploit to further investigate its potential in cancer treatment. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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8 pages, 481 KiB

Open AccessReview

Snake Venoms in Cancer Therapy: Past, Present and Future

by Li Li, Jianzhong Huang and Yao Lin

Toxins 2018, 10(9), 346; https://doi.org/10.3390/toxins10090346 - 29 Aug 2018

Cited by 56 | Viewed by 12863

Abstract

Cancer is one of the leading causes of morbidity and mortality worldwide, and the discovery of new drugs for cancer therapy is one of the most important objectives for the pharmaceutical industry. Snake venoms are complex mixtures containing different peptides, proteins, enzymes, carbohydrates [...] Read more.

Cancer is one of the leading causes of morbidity and mortality worldwide, and the discovery of new drugs for cancer therapy is one of the most important objectives for the pharmaceutical industry. Snake venoms are complex mixtures containing different peptides, proteins, enzymes, carbohydrates and other bioactive molecules, which are secreted by the snake in the predation or defending against threats. Understanding the snake venoms may turn the toxins into a valuable source of new lead compounds in drug discovery. Captopril, the first angiotensin-converting enzyme inhibitor approved in 1981 by FDA, was designed based on the structure of a peptide isolated from the snake venom. The earliest reports about snake venoms used in cancer treatments appeared in the 1930s. Since then, numerous studies on the activities, isolations, purifications and structure elucidations of the components from snake venoms were published. The comprehensive structural and functional investigations of snake venoms would contribute to the development of novel anti-cancer drugs. Our review will focus on the past, present and the future of the studies on snake venoms in cancer target therapy. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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14 pages, 920 KiB

Open AccessReview

The Development of Toad Toxins as Potential Therapeutic Agents

by Ji Qi, Abu Hasanat Md Zulfiker, Chun Li, David Good and Ming Q. Wei

Toxins 2018, 10(8), 336; https://doi.org/10.3390/toxins10080336 - 20 Aug 2018

Cited by 56 | Viewed by 8375

Abstract

Toxins from toads have long been known to contain rich chemicals with great pharmaceutical potential. Recent studies have shown more than 100 such chemical components, including peptides, steroids, indole alkaloids, bufogargarizanines, organic acids, and others, in the parotoid and skins gland secretions from [...] Read more.

Toxins from toads have long been known to contain rich chemicals with great pharmaceutical potential. Recent studies have shown more than 100 such chemical components, including peptides, steroids, indole alkaloids, bufogargarizanines, organic acids, and others, in the parotoid and skins gland secretions from different species of toads. In traditional Chinese medicine (TCM), processed toad toxins have been used for treating various diseases for hundreds of years. Modern studies, including both experimental and clinical trials, have also revealed the molecular mechanisms that support the development of these components into medicines for the treatment of inflammatory diseases and cancers. More recently, there have been studies that demonstrated the therapeutic potential of toxins from other species of toads, such as Australian cane toads. Previous reviews mostly focused on the pharmaceutical effects of the whole extracts from parotoid glands or skins of toads. However, to fully understand the molecular basis of toad toxins in their use for therapy, a comprehensive understanding of the individual compound contained in toad toxins is necessary; thus, this paper seeks to review the recent studies of some typical compounds frequently identified in toad secretions. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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10 pages, 942 KiB

Open AccessReview

Bouganin, an Attractive Weapon for Immunotoxins

by Massimo Bortolotti, Andrea Bolognesi and Letizia Polito

Toxins 2018, 10(8), 323; https://doi.org/10.3390/toxins10080323 - 8 Aug 2018

Cited by 15 | Viewed by 4481

Abstract

Bougainvillea (Bougainvillea spectabilis Willd.) is a plant widely used in folk medicine and many extracts from different tissues of this plant have been employed against several pathologies. The observation that leaf extracts of Bougainvillea possess antiviral properties led to the purification and [...] Read more.

Bougainvillea (Bougainvillea spectabilis Willd.) is a plant widely used in folk medicine and many extracts from different tissues of this plant have been employed against several pathologies. The observation that leaf extracts of Bougainvillea possess antiviral properties led to the purification and characterization of a protein, named bouganin, which exhibits typical characteristics of type 1 ribosome-inactivating proteins (RIPs). Beyond that, bouganin has some peculiarities, such as a higher activity on DNA with respect to ribosomal RNA, low systemic toxicity, and immunological properties quite different than other RIPs. The sequencing of bouganin and the knowledge of its three-dimensional structure allowed to obtain a not immunogenic mutant of bouganin. These features make bouganin a very attractive tool as a component of immunotoxins (ITs), chimeric proteins obtained by linking a toxin to a carrier molecule. Bouganin-containing ITs showed very promising results in the experimental treatment of both hematological and solid tumors, and one bouganin-containing IT has entered Phase I clinical trial. In this review, we summarize the milestones of the research on bouganin such as bouganin chemico-physical characteristics, the structural properties and de-immunization studies. In addition, the in vitro and in vivo results obtained with bouganin-containing ITs are summarized. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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