Functional, immunological characterization, and anticancer activity of BaMtx: A new Lys49- PLA2 homologue isolated from the venom of Peruvian Bothrops atrox snake (Serpentes: Viperidae)

Proleón, Alex; Torrejón, Daniel; Urra, Félix A.; Lazo, Fanny; López-Torres, Camila; Fuentes-Retamal, Sebastián; Quispe, Edwin; Bautista, Lorgio; Agurto, Andrés; Gavilán, Ronnie G.; Sandoval, Gustavo A.; Rodríguez, Edith; Sanchez, Eládio Flores; Yarlequé, Armando; Vivas-Ruiz, Dan

doi:10.1016/j.ijbiomac.2022.03.111

Cited by 11 publications

(12 citation statements)

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“…This mechanism may explain the selective effect of PLA2s on tumor mitochondria and highlight their potential anticancer as Proleón et al. ( 45 ) have reported ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 52%

Section: Bamtxmentioning

confidence: 99%

“…Induction of myotoxicity and production of edema (45). Mild anti-proliferative and antimigratory effects on breast cancer cells, affecting the ROS and NADH levels, reducing the mitochondrial respiration (45). Crotamine Isolated from Crotalus durissus terrificus venom 4.8 kDa highly basic (pI = 10.3) cellpenetrating myotoxin (42 aa) (43,44).…”

Section: Bamtxmentioning

confidence: 99%

“…BaMtx is a 13 kDa Lys49-PLA2 homologue with high myotoxic activity 45 ). This effect is attributed to cationic residues in the conserved C-terminal region ( 109 ), which electrostatically interacts with negatively charged residues in the cellular membrane collapsing the membrane organization ( 110 ).…”

Section: Introductionmentioning

confidence: 99%

“…This mechanism could be the basis for the mild anti-proliferative and anti-migratory effects showed BaMtx on breast cancer cells. A possible mechanism dependent on mitochondrial bioenergetics was recently hypothesized ( 45 ). BaMtx may increase a fast Ca 2+ influx, producing oxidative stress that reduces the electron donor NADH for Complex I activity, reducing basal mitochondrial respiration and consequently the precursors required for G1/S-cell cycle transition as have been described for proliferating cancer cells ( 112 , 113 ).…”

Section: Introductionmentioning

confidence: 99%

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An Emergent Role for Mitochondrial Bioenergetics in the Action of Snake Venom Toxins on Cancer Cells

et al. 2022

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Beyond the role of mitochondria in apoptosis initiation/execution, some mitochondrial adaptations support the metastasis and chemoresistance of cancer cells. This highlights mitochondria as a promising target for new anticancer strategies. Emergent evidence suggests that some snake venom toxins, both proteins with enzymatic and non-enzymatic activities, act on the mitochondrial metabolism of cancer cells, exhibiting unique and novel mechanisms that are not yet fully understood. Currently, six toxin classes (L-amino acid oxidases, thrombin-like enzymes, secreted phospholipases A2, three-finger toxins, cysteine-rich secreted proteins, and snake C-type lectin) that alter the mitochondrial bioenergetics have been described. These toxins act through Complex IV activity inhibition, OXPHOS uncoupling, ROS-mediated permeabilization of inner mitochondrial membrane (IMM), IMM reorganization by cardiolipin interaction, and mitochondrial fragmentation with selective migrastatic and cytotoxic effects on cancer cells. Notably, selective internalization and direct action of snake venom toxins on tumor mitochondria can be mediated by cell surface proteins overexpressed in cancer cells (e.g. nucleolin and heparan sulfate proteoglycans) or facilitated by the elevated Δψm of cancer cells compared to that non-tumor cells. In this latter case, selective mitochondrial accumulation, in a Δψm-dependent manner, of compounds linked to cationic snake peptides may be explored as a new anti-cancer drug delivery system. This review analyzes the effect of snake venom toxins on mitochondrial bioenergetics of cancer cells, whose mechanisms of action may offer the opportunity to develop new anticancer drugs based on toxin scaffolds.

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“…This mechanism may explain the selective effect of PLA2s on tumor mitochondria and highlight their potential anticancer as Proleón et al. ( 45 ) have reported ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 52%

Section: Bamtxmentioning

confidence: 99%