Identification of anti-tumor components from toad venom

Gao, Fei; Wang, Xiangjun; Li, Zhao; Zhou, Aicun; Tiffany‐Castiglioni, Evelyn; Xie, Lijun; Qian, Yongchang

doi:10.3892/ol.2017.6160

Cited by 12 publications

(18 citation statements)

References 31 publications

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“…These compounds are responsible for a large panel of potential therapeutic indications such as cardiotonic/anti-arrhythmic, antidiabetic, immunomodulatory, antibacterial/antifungal, antiprotozoal, antiviral, antineoplastic, sleep inducing, analgesic, contraceptive, endocrine activity, behavioral changes or wound healing [19,20]. Among antiproliferative activities, some specific ones have already been highlighted on melanoma cells [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the Compounds of Two Different Venoms

Soumoy

Wells

Najem

et al. 2020

Biology

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Melanoma is the most common cancer in young adults, with a constantly increasing incidence. Metastatic melanoma is a very aggressive cancer with a 5-year survival rate of about 22−25%. This is, in most cases, due to a lack of therapies which are effective on the long term. Hence, it is crucial to find new therapeutic agents to increase patient survival. Toad venoms are a rich source of potentially pharmaceutically active compounds and studies have highlighted their possible effect on cancer cells. We focused on the venoms of two different toad species: Bufo bufo and Rhinella marina. We screened the venom crude extracts, the fractions from crude extracts and isolated biomolecules by studying their antiproliferative properties on melanoma cells aiming to determine the compound or the combination of compounds with the highest antiproliferative effect. Our results indicated strong antiproliferative capacities of toad venoms on melanoma cells. We found that these effects were mainly due to bufadienolides that are cardiotonic steroids potentially acting on the Na+/K+ ATPase pump which is overexpressed in melanoma. Finally, our results indicated that bufalin alone was the most interesting compound among the isolated bufadienolides because it had the highest antiproliferative activity on melanoma cells.

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Section: Introductionmentioning

confidence: 99%

Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the Compounds of Two Different Venoms

Soumoy

Wells

Najem

et al. 2020

Biology

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“…These additional copies may produce neofunctionalization or subfunctionalization, which could have provided the genetic basis for new functional generation. For example, one primary active component of toad toxins is Bufalin, a cardiotonic steroid (Gao et al, 2017). The Cyp family is responsible for steroid hormone biosynthesis; therefore, it is reasonable to speculate that some of the expanded Cyp gene members may be crucial for Bufalin biosynthesis, suggesting that their mRNA regulation is essential for toad toxin-producing tissues.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and gene-family dynamic analyses reveal gene expression pattern and evolution in toxin-producing tissues of Asiatic toad (Bufo gargarizans)

Li²,

Wen³

et al. 2022

Front. Ecol. Evol.

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Comprising a major clade of Anura, toads produce and secrete numerous toxins from both the parotoid glands behind their eyes and their dorsal skin. These toxins, made of various proteins and compounds, possess pharmacological potential to be repurposed to benefit human health. However, the detailed genetic regulation of toad toxin production is still poorly understood. A recent publication uncovering the genome of the representative Asiatic toad (Bufo gargarizans) provides a good reference to resolve this issue. In the present study, we sequenced the transcriptomes of parotoid gland, dorsal skin and liver from the Asiatic toad. Combining our data with 35 previously published transcriptomes across eight different tissues from the same species but from different locations, we constructed a comprehensive gene co-expression network of the Asiatic toad with the assistance of the reference genome assembly. We identified 2,701 co-expressed genes in the toxin-producing tissues (including parotoid gland and dorsal skin). By comparative genomic analysis, we identified 599 expanded gene families with 2,720 genes. Through overlapping these co-expressed genes in the toad toxin-producing tissues, we observed that three cytochrome P450 (Cyp) family members (Cyp27a1, Cyp2c29, and Cyp2c39) were significantly enriched in pathways related to cholesterol metabolism. Cholesterol is a critical precursor to steroids, and the known main steroidal toxins of bufadienolides are considered as the major bioactive components in the parotoid glands of Asiatic toad. We found 3-hydroxy-methylglutaryl CoA reductase (hmgcr), encoding the major rate-limiting enzyme for cholesterol biosynthesis, appears with multiple copies in both Asiatic toad and common toad, possibly originating from a tandem duplication event. The five copies of hmgcr genes consistently displayed higher transcription levels in the parotoid gland when compared with the abdominal skin, suggesting it as a vital candidate gene in the involvement of toad toxin production. Taken together, our current study uncovers transcriptomic and gene-family dynamic evidence to reveal the vital role of both expanded gene copies and gene expression changes for production of toad toxins.

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“…For these reasons, these compounds may serve as leads for developing novel heart medications and analgesics. Furthermore, preparations from anuran venoms including toad cake showed encouraging in vitro antitumor activity that might be associated with the inhibition of cell proliferation, the promotion of angiogenesis of tumor endothelial cells, the induction of apoptosis, the promotion of differentiation, and the stimulation of tumor-directed immune responses [72][73][74]. Comparable results were obtained with various isolated bufadienolides [72][73][74].…”

Section: Bioactive Compounds From Anuramentioning

confidence: 99%

Exploring the global animal biodiversity in the search for new drugs -Amphibians

Mans¹,

Pawirodihardjo²,

Djotaroeno³

et al. 2021

J Transl Sci

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Many breakthrough drugs have been developed from plants with medicinal properties on the basis of ethnopharmacological information. In the search for structurally novel and mechanistically unique lead compounds, drug discovery and development progams are now also paying attention to the myriad of bioactive molecules provided by the animal biodiversity. A well-known example emerging from these efforts is the breakthrough angiotensin-converting enzyme inhibitor captopril used for the treatment of hypertension and congestive heart failure. Captopril has been developed as an analogue of bradykinin in the venom of the Brazilian pit viper Bothrops jararaca (Viperidae) following the observation that the latter agent lowered blood pressure by vasodilation. In the mean time, dozens of clinically useful and potentially therapaeutically applicable compounds from animal origin have been identified. The skin gland secretions of amphibians have been refined during millions of years of evolution to highly efficient defensive chemicals. These compounds have remarkable pharmacological activities and may also represent a treasure chest of potentially novel drugs against pathophysiological conditions. This paper addresses the importance of bioactive compounds in the skin secretions of frogs, toads, salamanders, newts, and caecilians, and elaborates on the therapeutic potential of some of them as anti-alzheimer, cardiotonic, antidiabetic, anti-HIV, analgesic, antimicrobial, and antiparasitic compounds.Mans DRA (2020) Exploring the global animal biodiversity in the search for new drugs -Amphibians

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Identification of anti-tumor components from toad venom

Cited by 12 publications

References 31 publications

Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the Compounds of Two Different Venoms

Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the Compounds of Two Different Venoms

Transcriptomic and gene-family dynamic analyses reveal gene expression pattern and evolution in toxin-producing tissues of Asiatic toad (Bufo gargarizans)

Exploring the global animal biodiversity in the search for new drugs -Amphibians

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