Anti-Breast Cancer Activity of Latroeggtoxin-V Mined from the Transcriptome of Spider Latrodectus tredecimguttatus Eggs

Xu, Donghui; Tang, Xiaochao; Wu, Xinzhou; Yu, Dianmei; Tang, Ping-Ping; Wang, Xianchun

doi:10.3390/toxins10110451

Cited by 8 publications

(6 citation statements)

References 51 publications

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“…To date, many anticancer peptides have been screened from animal venom. For example, the spider polypeptide latroeggtoxin-V inhibits the proliferation, migration, and cell cycle of breast cancer MDA-MB-231 cells in a concentration-dependent manner ( Xu et al, 2018 ). Melittin, the main peptide component of Apis mellifera venom, inhibits EGF-induced cell movement and invasion by inhibiting the PI3K/Akt/mTOR signalling pathway in breast cancer cells ( Lim et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Yin

Feng

et al. 2023

Front. Pharmacol.

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Nav1.5 channel is crucial for the proliferation and migration of breast cancer cells. In this study, we investigated the anticancer effect of JZTX-14, a natural peptide considered an effective antagonist of Nav1.5. First, we successfully isolated and purified the 31 amino acid peptide JZTX-14 containing three pairs of disulfide bonds from spider venom and synthesised JZTX-14 by solid phase synthesis. We then predicted their physiochemical properties and structures in the peptide database. Further, we investigated the effects of natural and synthetic JZTX-14 on the proliferation and migration of MDA-MB-231 breast cancer cells via modulation of sodium current through the Nav1.5 channel. The results showed that both synthetic and natural JZTX-14 inhibited Nav1.5 currents, indicating the successful synthesis of JZTX-14. However, JZTX-14 did not affect MDA-MB-231 cell proliferation but inhibited its migration. Transcriptome analysis revealed that JZTX-14 downregulated S100A4 and FBXO2 and upregulated SERPINB2 in MDA-MB-231 cells. Western blot analysis demonstrated an increased level of the epithelial marker, E-cadherin, and decreased levels of the mesenchymal markers, N-cadherin and vimentin, and matrix metalloproteinase (MMP2), indicating the possible underlying mechanism of the inhibition of MDA-MB-231 cell migration by JZTX-14. This study provides a new target for inhibiting breast cancer metastasis and identifies a potent natural peptide for treating Triple-negative breast cancer.

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Section: Discussionmentioning

confidence: 99%

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Yin

Feng

et al. 2023

Front. Pharmacol.

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“…A few articles analyzed the antitumor action of components from widow spiders' venom and eggs. The recombinant latroeggtoxin-V inhibits the proliferation and migration of breast cancer cells (MDA-MB-231) and also causes their apoptosis; the toxin inhibits the activity of the Na + /K + -ATPase in a concentration-dependent manner, suggesting that its action affects ion transport [218].…”

Section: Antitumor Activitymentioning

confidence: 99%

Widow spiders in the New World: a review on Latrodectus Walckenaer, 1805 (Theridiidae) and latrodectism in the Americas

Caruso

Lauria

Souza

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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Humankind has always been fascinated by venomous animals, as their toxic substances have transformed them into symbols of power and mystery. Over the centuries, researchers have been trying to understand animal venoms, unveiling intricate mixtures of molecules and their biological effects. Among venomous animals, Latrodectus Walckenaer, 1805 (widow spiders) have become feared in many cultures worldwide due to their extremely neurotoxic venom. The Latrodectus genus encompasses 32 species broadly spread around the globe, 14 of which occur in the Americas. Despite the high number of species found in the New World, the knowledge on these spiders is still scarce. This review covers the general knowledge on Latrodectus spp. from the Americas. We address widow spiders' taxonomy; geographical distribution and epidemiology; symptoms and treatments of envenomation (latrodectism); venom collection, experimental studies, proteome and transcriptome; and biotechnological studies on these Latrodectus spp. Moreover, we discuss the main challenges and limitations faced by researchers when trying to comprehend this neglected group of medically important spiders. We expect this review to help overcome the lack of information regarding widow spiders in the New World.

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“…In the transcriptome analysis of the L.tredecimguttatus eggs, Xu et al found a series of genes that encode proteinaceous toxins, two of which were named latroeggtoxin‐V and latroeggtoxin‐VI, respectively (Xu and Wang 2016). Latroeggtoxin‐V was shown to selectively inhibit breast cancer cell lines MDA‐MB‐231 by affecting the activity of Na + /K + ‐ATPase (Xu et al 2018) Latroeggtoxin‐VI (LETX‐VI) can increase the levels of total and released dopamine in PC12 cells, which is influenced by extracellular Ca 2+ and, however, the exact underlying molecular mechanism has not been fully clear (Tang et al 2021a).…”

Section: Introductionmentioning

confidence: 99%

Insights into the mediation of Ca2+ signaling in the promoting effects of LETX-VI on the synthesis and release of dopamine

Lei,

Wang,

Zhai

et al. 2023

J. Cell Commun. Signal.

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Latroeggtoxin-VI (LETX-VI) is an active protein and was previously demonstrated to have effects on the synthesis and release of dopamine. Hererin, the involvement of Ca 2+ signaling in the effects of LETX-VI on dopamine was systematically investigated, using PC12 cells as a neuron model. LETX-VI was shown to promote dopamine release from PC12 cells both in the presence and absence of extracellular Ca 2+ ; however the presence of extracellular Ca 2+ was favorable for enhancing the promoting effects of LETX-VI on dopamine, because LETX-VI facilitated the influx of extracellular Ca 2+ through the L-type calcium channels in plasma membrane (PM) to increase cytosolic Ca 2+ concentration. LETX-VI was able to penetrate the PM of PC12 cells to act on the Ca 2+ channel proteins IP3Rs and RyRs in the endoplasm reticulum (ER) membrane, opening the Ca 2+ channels and promoting the release of ER Ca 2+ to elevate cytosolic Ca 2+ level. With the help of intracellular Ca 2+ chelator BAPTA, the elevated cytosolic Ca 2+ level was proven to play crucial role for the enhanced promoting effects of LETX-VI on dopamine. Taken together, LETX-VI is able to open the Ca 2+ channels in both PM and ER membrane simultaneously to facilitate extracellular Ca 2+ influx and ER Ca 2+ release, and thus increases the cytosolic Ca 2+ concentration to enhance the promoting effects on the synthesis and release of dopamine.

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Anti-Breast Cancer Activity of Latroeggtoxin-V Mined from the Transcriptome of Spider Latrodectus tredecimguttatus Eggs

Cited by 8 publications

References 51 publications

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels

Widow spiders in the New World: a review on Latrodectus Walckenaer, 1805 (Theridiidae) and latrodectism in the Americas

Insights into the mediation of Ca2+ signaling in the promoting effects of LETX-VI on the synthesis and release of dopamine

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