Phase I study of VRCTC-310, a purified phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data

Costa, Luís; Miles, Horacio A.; Díez, Roberto A.; Araujo, Carlos E.; Molina, Carlos Martin; Cervellino, Juan C.

doi:10.1097/00001813-199710000-00003

Cited by 26 publications

(17 citation statements)

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“…Crotoxin, a pre-synaptic neurotoxin has been tried as an anti-cancer agent in advanced cancer patients [31]. VRCTC-310, a natural product with PLA 2 from Crotalus Durissus terrificus and cardiotoxin from Naja Naja atra , have inhibitory effect against human and murine tumor cell lines, and have effective value in the treatment of advanced solid cancers, which were refractory to other therapy [32]. …”

Section: Resultsmentioning

confidence: 99%

Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review

Meenakshisundaram

Shah

Thirumalaikolundusubramanian³

2009

AIDS Res Ther

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BackgroundSnake and insect venoms have been demonstrated to have beneficial effects in the treatment of certain diseases including drug resistant human immunodeficiency virus (HIV) infection. We evaluated and hypothesized the probable mechanisms of venoms against HIV.MethodsPrevious literatures published over a period of 30 years (1979-2009) were searched using the key words snake venom, insect venom, mechanisms and HIV. Mechanisms were identified and discussed.Results & ConclusionWith reference to mechanisms of action, properties and components of snake venom such as sequence homology and enzymes (protease or L- amino acid oxidase) may have an effect on membrane protein and/or act against HIV at multiple levels or cells carrying HIV virus resulting in enhanced effect of anti-retroviral therapy (ART). This may cause a decrease in viral load and improvement in clinical as well as immunological status. Insect venom and human Phospholipase A2 (PLA2) have potential anti-viral activity through inhibition of virion entry into the cells. However, all these require further evaluation in order to establish its role against HIV as an independent one or as a supplement.

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Section: Resultsmentioning

confidence: 99%

Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review

Meenakshisundaram

Shah

Thirumalaikolundusubramanian³

2009

AIDS Res Ther

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“…Data from Zhao et al indicated that snake venom secreted phospholipase A 2 (sPLA 2 ) induced apoptosis in Mv1Lu cells in a dose-and timedependent manner, and was associated with a rapid increase in intracellular ceramide level [39] . The clinical trial using snake venom and their active components have succeeded in cancer therapies, but its application was confined to the auxiliary treatment of patients in the late stage [40,41] . Its toxic and side effects were unavoidable.…”

Section: Discussionmentioning

confidence: 99%

Serum from rabbit orally administered cobra venom inhibits growth of implanted hepatocellular carcinoma cells in mice

Sun¹,

Ren²,

Zhang³

et al. 2003

WJG

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AIM:To investigate the inhibitory effect of serum preparation from rabbits orally administered cobra venom (SRCV) on implanted hepatocellular carcinoma (HCC) cells in mice. METHODS:An HCC cell line, HepA, was injected into mice to prepare implanted tumors. The animals (n=30) were divided randomly into SRCV, 5-fluorouracil (5-FU), and distilled water (control) groups. From the second day after transplantation, 20 mg/kg 5-FU was administered intraperitoneally once a day for 9 days. SRCV (1 000 mg/kg) or distilled water (0.2 mL) was given by gastrogavage. Tumor growth inhibition was described by the inhibitory rate (IR). Apoptosis was detected by transmission electron microscopy (TEM), flow cytometry (FCM), and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Student's t-test was performed for statistical analysis. RESULTS:The tumor growth was inhibited markedly by SRCV treatment compared to that in the control group (P<0.01). The treatment resulted in a significant increase in the apoptotic rate of cancer cells by the factors of 10.5±2.4 % and 20.65±3.2 % as demonstrated through TUNEL and FCM assays, respectively (P<0.01). The apoptotic cells were also identified by characteristic ultrastructural features. CONCLUSION: SRCV can inhibit the growth of implantedHepA cells in mice, and the apoptosis rate appears to elevate during the process. Sun P, Ren XD, Zhang HW, Li XH, Cai SH, Ye KH, Li XK. Serum from rabbit orally administered cobra venom inhibits growth of implanted hepatocellular carcinoma cells in mice.

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“…Se ha evaluado el efecto anticancerígeno de diversas toxinas y venenos ofídicos, como fuentes de nuevas moléculas en la lucha contra el cáncer (35)(36)(37)(38)(39). Además, la citotoxicidad de los venenos y las fosfolipasas A2 resulta ser un problema para su futuro uso biomédico.…”

Section: Identificación De Proteínasunclassified

“…Además de su citotoxicidad, el efecto anticancerígeno de estas toxinas podría estar relacionado con autofagia de las células tumorales (40). La escasa toxicidad y la ausencia de neurotoxicidad residual de la crotoxina B en estudios con animales, refuerzan su uso en seres humanos como ya ha sido previamente demostrado (35,36,41).…”

Section: Identificación De Proteínasunclassified

Efecto citotóxico de fosfolipasas A2 del veneno de Crotalus durissus cumanensis de Colombia

Quintana-Castillo¹,

Ávila-Gómez²,

Ceballos-Ruiz³

et al. 2017

Revista Investig. Salud Univ. Boyacá

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RESUMENIntroducción. Los venenos de serpientes representan una fuente importante de proteínas y péptidos, los cuales exhiben diversas actividades biológicas, tales como antibacterianas, antiparasitarias, antivirales, antitumorales, antifúngicas y contra la agregación plaquetaria, entre otras.Las fosfolipasas A2 presentes en los venenos de serpientes son las proteínas más estudiadas en estos modelos. Se ha demostrado que las fosfolipasas A2, activas e inactivas, poseen actividad catalítica contra células tumorales.Objetivo. Aislar, purificar y caracterizar la fosfolipasa A2 del veneno de Crotalus durissus cumanensis para evaluar su actividad antitumoral in vitro.Materiales y métodos. El aislamiento, la purificación y la identificación de la crotoxina B se hizo mediante la cromatografía de exclusión molecular, la cromatografía líquida de alto rendimiento de fase inversa (Reversed Phase High-Performance Liquid Chromatography, RP-HPLC) y la espectrometría de masas. El efecto citotóxico sobre células tumorales (K562) y células normales (células mononucleares de sangre periférica) se determinó utilizando la técnica de MTT.Resultados. La separación y posterior identificación de la crotoxina B del veneno de C. d. cumanensis de Colombia, permitieron evidenciar que esta fosfolipasa A2 posee efecto citotóxico sobre las células mononucleares de sangre periférica con una dosis de 18,23 ± 0,57 µg/ml, mientras que, para las células K562, fue de 2,34 ± 0,199 µg/ml.Conclusiones. Los resultados sugieren la posibilidad de utilizar la crotoxina B aislada del veneno de C.d. cumanensis como un posible recurso terapéutico para su aplicación en humanos.

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Phase I study of VRCTC-310, a purified phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data

Cited by 26 publications

References 0 publications

Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review

Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review

Serum from rabbit orally administered cobra venom inhibits growth of implanted hepatocellular carcinoma cells in mice

Efecto citotóxico de fosfolipasas A2 del veneno de Crotalus durissus cumanensis de Colombia

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