Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography
Snake venoms constitute a complex, rapidly evolving trait, whose composition varies between and within populations depending on geographical location, age and preys (diets). These factors have determined the adaptive evolution for predatory success and link venom heterogeneity with prey specificity....
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MDPI AG
2023-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/9/549 |
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| author | Bianca Op den Brouw Manuel A. Fernandez-Rojo Tom Charlton Bryan G. Fry Maria P. Ikonomopoulou |
| author_facet | Bianca Op den Brouw Manuel A. Fernandez-Rojo Tom Charlton Bryan G. Fry Maria P. Ikonomopoulou |
| author_sort | Bianca Op den Brouw |
| collection | DOAJ |
| description | Snake venoms constitute a complex, rapidly evolving trait, whose composition varies between and within populations depending on geographical location, age and preys (diets). These factors have determined the adaptive evolution for predatory success and link venom heterogeneity with prey specificity. Moreover, understanding the evolutionary drivers of animal venoms has streamlined the biodiscovery of venom-derived compounds as drug candidates in biomedicine and biotechnology. The king cobra (<i>Ophiophagus hannah</i>; Cantor, 1836) is distributed in diverse habitats, forming independent populations, which confer differing scale markings, including between hatchlings and adults. Furthermore, king cobra venoms possess unique cytotoxic properties that are used as a defensive trait, but their toxins may also have utility as promising anticancer-agent candidates. However, the impact of geographical distribution and age on these potential venom applications has been typically neglected. In this study, we hypothesised that ontogenetic venom variation accompanies the morphological distinction between hatchlings and adults. We used non-transformed neonatal foreskin (NFF) fibroblasts to examine and compare the variability of venom cytotoxicity between adult captive breeding pairs from Malaysian and Chinese lineages, along with that of their progeny upon hatching. In parallel, we assessed the anticancer potential of these venoms in human-melanoma-patient-derived cells (MM96L). We found that in a geographical distribution and gender-independent manner, venoms from hatchlings were significantly less cytotoxic than those from adults (NFF; ~Log EC<sub>50</sub>: 0.5–0.6 vs. 0.2–0.35 mg/mL). This is consistent with neonates occupying a semifossorial habitat, while adults inhabit more above-ground habitats and are therefore more conspicuous to potential predators. We also observed that Malaysian venoms exhibited a slightly higher cytotoxicity than those from the Chinese cobra cohorts (NFF; Log EC<sub>50</sub>: 0.1–0.3 vs. 0.3–0.4 mg/mL), which is consistent with Malaysian king cobras being more strongly aposematically marked. These variations are therefore suggestive of differential anti-predator strategies associated with the occupation of distinct niches. However, all cobra venoms were similarly cytotoxic in both melanoma cells and fibroblasts, limiting their potential medical applications in their native forms. |
| first_indexed | 2024-03-10T21:54:03Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T21:54:03Z |
| publishDate | 2023-09-01 |
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| series | Toxins |
| spelling | doaj.art-dc87d7305c3948069d2b89dffc1e8ebb2023-11-19T13:15:54ZengMDPI AGToxins2072-66512023-09-0115954910.3390/toxins15090549Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and GeographyBianca Op den Brouw0Manuel A. Fernandez-Rojo1Tom Charlton2Bryan G. Fry3Maria P. Ikonomopoulou4Venom Evolution Lab, School of Biological Sciences, The University of Queensland, Brisbane, QLD 4072, AustraliaHepatic Regenerative Medicine Group, Madrid Institute for Advanced Studies in Food, E28049 Madrid, SpainDepartment of Natural Sciences, Manchester Metropolitan University, All Saints Building, Manchester M15 6BH, UKVenom Evolution Lab, School of Biological Sciences, The University of Queensland, Brisbane, QLD 4072, AustraliaTranslational Venomics Group, Madrid Institute for Advanced Studies in Food, E28049 Madrid, SpainSnake venoms constitute a complex, rapidly evolving trait, whose composition varies between and within populations depending on geographical location, age and preys (diets). These factors have determined the adaptive evolution for predatory success and link venom heterogeneity with prey specificity. Moreover, understanding the evolutionary drivers of animal venoms has streamlined the biodiscovery of venom-derived compounds as drug candidates in biomedicine and biotechnology. The king cobra (<i>Ophiophagus hannah</i>; Cantor, 1836) is distributed in diverse habitats, forming independent populations, which confer differing scale markings, including between hatchlings and adults. Furthermore, king cobra venoms possess unique cytotoxic properties that are used as a defensive trait, but their toxins may also have utility as promising anticancer-agent candidates. However, the impact of geographical distribution and age on these potential venom applications has been typically neglected. In this study, we hypothesised that ontogenetic venom variation accompanies the morphological distinction between hatchlings and adults. We used non-transformed neonatal foreskin (NFF) fibroblasts to examine and compare the variability of venom cytotoxicity between adult captive breeding pairs from Malaysian and Chinese lineages, along with that of their progeny upon hatching. In parallel, we assessed the anticancer potential of these venoms in human-melanoma-patient-derived cells (MM96L). We found that in a geographical distribution and gender-independent manner, venoms from hatchlings were significantly less cytotoxic than those from adults (NFF; ~Log EC<sub>50</sub>: 0.5–0.6 vs. 0.2–0.35 mg/mL). This is consistent with neonates occupying a semifossorial habitat, while adults inhabit more above-ground habitats and are therefore more conspicuous to potential predators. We also observed that Malaysian venoms exhibited a slightly higher cytotoxicity than those from the Chinese cobra cohorts (NFF; Log EC<sub>50</sub>: 0.1–0.3 vs. 0.3–0.4 mg/mL), which is consistent with Malaysian king cobras being more strongly aposematically marked. These variations are therefore suggestive of differential anti-predator strategies associated with the occupation of distinct niches. However, all cobra venoms were similarly cytotoxic in both melanoma cells and fibroblasts, limiting their potential medical applications in their native forms.https://www.mdpi.com/2072-6651/15/9/549cobra snakesanimal venomcytotoxicity |
| spellingShingle | Bianca Op den Brouw Manuel A. Fernandez-Rojo Tom Charlton Bryan G. Fry Maria P. Ikonomopoulou Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography Toxins cobra snakes animal venom cytotoxicity |
| title | Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography |
| title_full | Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography |
| title_fullStr | Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography |
| title_full_unstemmed | Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography |
| title_short | Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography |
| title_sort | malaysian and chinese king cobra venom cytotoxicity in melanoma and neonatal foreskin fibroblasts is mediated by age and geography |
| topic | cobra snakes animal venom cytotoxicity |
| url | https://www.mdpi.com/2072-6651/15/9/549 |
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