Snake venom L-amino acid oxidases: an overview on their antitumor effects

Costa, Tássia R.; Burin, Sandra Mara; Menaldo, Danilo L.; Castro, Fabíola Attié de; Sampaio, Suely Vilela

doi:10.1186/1678-9199-20-23

Cited by 81 publications

(55 citation statements)

References 56 publications

(91 reference statements)

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“…However, of particular interest in AAOs are the l-amino acid oxidases (LAAOs) because AAOs are highly speciic for l-amino acids, and generally hydrophobic amino acids (such as phenylalanine, tryptophan, tyrosine and leucine) [24] are the best substrates [25]. These lavoenzymes are found in diverse organisms, such as bacteria, fungi, algae, ish, snails as well as venoms of snake families [26].…”

Section: Amino Acid Oxidasesmentioning

confidence: 99%

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Therapeutic Uses of Amino Acids

Odia¹,

Esezobor²

2017

Amino Acid - New Insights and Roles in Plant and Animal

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Amino acids, which are the building blocks of peptides and proteins, are indispensable chemicals needed by the body for optimal metabolism and proper body functioning. Classiied as essential, nonessential and conditionally essential, amino acids play vital roles in the body such as in protein synthesis and as precursors in the production of secondary metabolism molecules. Amino acid oxygenases also play vital metabolic roles such as in prevention of diseases; as a result, amino acids and their oxygenases isolated from various organisms are potent candidates in treatment of diseases which include cancers, inlammations, as well as antibacterial agents.

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Section: Amino Acid Oxidasesmentioning

confidence: 99%

“…The venoms of many snakes have characteristic yellow colour which has been atributed to the lavin component in LAAOs isolated from the snakes. The lavins have also been reported to contribute to the toxicity of such venoms because of the oxidative stress caused by H 2 O 2 production [26].…”

Section: Amino Acid Oxidasesmentioning

confidence: 99%

Therapeutic Uses of Amino Acids

Odia¹,

Esezobor²

2017

Amino Acid - New Insights and Roles in Plant and Animal

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“…e A549, drasticamente reduzido (LI LEE et al, 2014). Portanto, podemos sugerir que o peróxido de hidrogênio produzido por essas toxinas, incluindo a CR-LAAO, está mesmo envolvido no mecanismo de ação citotóxica proposto para essa classe de toxinas (DU; CLEMETSON, 2002;GUO et al;IZIDORO et al, 2014;COSTA et al, 2014).…”

Section: Discussionunclassified

“…O iminoácido sofre hidrólise não enzimática liberando o α-cetoácido e amônia. Uma meia-reação oxidativa completa o ciclo reoxidando FADH2 com o oxigênio molecular produzindo peróxido de hidrogênio (Figura 1) (CURTI et al, 1992;KOMMOJU et al, 2007;LI et al, 2008;RODRIGUES et al, 2009;SUN et al, 2010;ALVES-PAIVA et al, 2011;COSTA et al, 2014).…”

Section: As L-aminoácido Oxidases (Laaos)unclassified

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Caracterização funcional e estudo dos mecanismos de resposta ao dano celular causado por uma L-aminoácido oxidase de Calloselasma rhodostoma em linhagens celulares humanas

Costa¹

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As L-aminoácido oxidases (LAAOs) isoladas de peçonhas de serpentes são alvos de um grande número de pesquisas devido às suas inúmeras ações biológicas e farmacológicas. O objetivo do presente trabalho foi caracterizar funcionalmente a Laminoácido oxidase da peçonha de Calloselasma rhodostoma (CR-LAAO) por meio das atividades: bactericida, fungicida, leishmanicida, tripanomicida, citotóxica, inflamatória e análise da expressão de genes e proteínas apoptóticas. A CR-LAAO mostrou-se altamente citotóxica sobre as células tumorais HepG2 e HL-60, promovendo cerca de 80% de morte celular na maior concentração testada (100 µg/mL) e apresentou baixa toxicidade sobre células PBMC. Foi possível observar que a proteína induziu apoptose (AV+) em PBMC. Em HepG2, as menores concentrações (0,1-2,5 µg/mL) causaram apoptose (AV+), e as maiores (5-100 µg/mL) causaram apoptose/necrose (PI+/AV+). Em HL-60, as concentrações testadas (0,1-100 µg/mL) induziram apoptose/necrose (PI+/AV+). A expressão do gene FAS e ativação das caspases 8 e 3 determinou a ativação da via extrínseca da apoptose na linhagem HL-60. A CR-LAAO promoveu algumas alterações na modulação do ciclo celular, sendo que nas linhagens tumorais os atrasos se concentraram nas fases G0/G1 e S do ciclo celular. Ademais, a CR-LAAO mostrouse bactericida contra as cepas S. aureus e E. coli, com maior especificidade para a cepa gram-positiva (S. aureus). Em análises de microscopia de transmissão, foi possível observar um desmantelamento da parede celular bacteriana. Após 6h de pré-incubação com C. albicans, a CR-LAAO foi capaz de inibir 80% do crescimento da levedura. A CR-LAAO mostrou-se também um bom agente leishmanicida contra as espécies L. infantum chagasi (IC50=16,66 µg/mL) e L. braziliensis (IC50=24,47 µg/mL) e inibiu o crescimento da forma promastigota do Trypanosoma cruzi (IC50=196,8 µg/mL). Testes in vivo revelaram que a CR-LAAO promoveu inflamação local aguda, recrutando células inflamatórias como neutrófilos e induzindo a formação de citocinas (IL-6 e IL-1β) e mediadores lipídicos (LTB4 e PGE2). Os resultados obtidos sugerem que a CR-LAAO apresenta potencial biotecnológico evidente, com efeitos antiparasitários, fungicida, bactericida, bem como atividade antitumoral in vitro. Dessa forma, os resultados obtidos para a CR-LAAO fornecem subsídios importantes para o desenvolvimento de estratégias terapêuticas de ação direcionada, como quimioterápicos e antimicrobianos mais eficazes.Palavras chaves: Calloselasma rhodostoma; L-aminoácido oxidase; apoptose; expressão gênica; atividade antiparasitária; bactericida; inflamação. L-amino acid oxidases (LAAOs) isolated from snake venoms are targets of a large number of researches due to their numerous biological and pharmacological actions. The objective of this study was to functionally characterize the L-amino acid oxidase from the venom of Calloselasma rhodostoma (CR-LAAO) through the activities: bactericidal, fungicidal, leishmanicidal, trypanocidal, cytotoxic, inflammatory and analysis of gene expression and apoptotic pro...

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Reactive oxygen species as a double‐edged sword: The role of oxidative enzymes in antitumor therapy

Rosini

Pollegioni

2021

BioFactors

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A number of approaches have been developed over the years to manage cancer, such as chemotherapy using low-molecular-mass molecules and radiotherapy. Here, enzymes can also find useful applications. Among them, oxidases have attracted attention because of their ability to produce reactive oxygen species (ROS, especially hydrogen peroxide) in tumors and potentially modulate the production of this cytotoxic compound when enzymes active on substrates present in low amounts are used, such as the D-amino acid oxidase and Damino acid couple system. These treatments have been also developed for additional cancer treatment approaches, such as phototherapy, nutrient starvation, and metal-induced hydroxyl radical production. In addition, to improve tumor specificity and decrease undesired side effects, oxidases have been targeted by means of nanotechnologies and protein engineering (i.e., by designing chimeric proteins able to accumulate in the tumor). The most recent advances obtained by using six different oxidases (i.e., the FAD-containing enzymes glucose oxidase, D-and L-amino acid oxidases, cholesterol oxidase and xanthine oxidase, and the copper-containing amine oxidase) have been reported. Anticancer therapy based on oxidase-based ROS production has now reached maturity and can be applied in the clinic.

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Snake venom L-amino acid oxidases: an overview on their antitumor effects

Cited by 81 publications

References 56 publications

Therapeutic Uses of Amino Acids

Therapeutic Uses of Amino Acids

Caracterização funcional e estudo dos mecanismos de resposta ao dano celular causado por uma L-aminoácido oxidase de Calloselasma rhodostoma em linhagens celulares humanas

Reactive oxygen species as a double‐edged sword: The role of oxidative enzymes in antitumor therapy

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