Abstract Cancer is the leading cause of death. Melanoma skin cancer originates in melanocytes and represents 80% of the deaths associated with skin cancer. Vinblastine (VIN) is a chemotherapeutic agent used in the treatment of cancer through disrupting mitotic spindle and tumor development. Curcumin (CUR), a compound extracted from the rhizomes of the Curcuma longa plant, has beneficial effects in preventing the development and progression of cancer while modulating the immune response and oxidative stress. The expression of purinergic receptors, ecto-enzymes, and adenosine can modulate the inflammatory responses in cancer. The activity of enzymes, the markers of cell damage in oxidative stress, the generation of reactive oxygen species (ROS), and the activities of ecto-enzymes in the melanoma cell line were investigated. The human melanoma cell line was treated with curcumin (40 µM), vinblastine (VIN) (20 nM), or a combination of both for 24h. Oxidative stress enzymes and byproducts were measured and compared against the activity of ecto-enzymes. There was a marked increase in ROS production in all groups, but an increase in protein carbonylation was only detected in the VIN group. CUR had an inhibitory effect on extracellular ADP hydrolysis, as evidenced by a significant decrease in ADP substrate removal. VIN possibly increased adenosine formation, as demonstrated by an increase in ADP substrate removal. VIN (alone or in combination with CUR) reduced the activity of ADA, thus increasing the concentration of adenosine in the tumor microenvironment. CUR increased ROS generation in melanoma cells and disrupted the purinergic signaling cascade. Therefore, it may be a promising adjuvant therapy for melanoma, a cancer with a high incidence and lethality.

RESUMO: O vírus da estomatite vesicular (vesicular stomatitis virus, VSV) é o agente de doença vesicular que afeta várias espécies e que, em suínos e ruminantes, é clinicamente confundível com a febre aftosa. Os equinos são particularmente susceptíveis ao VSV, servindo de sentinelas para a circulação viral. O presente trabalho investigou a presença de anticorpos neutralizantes contra o VSV Indiana III (VSIV-3) em amostras de soro de 3626 equinos de seis estados das regiões Sul (RS, n=1011), Centro-oeste (GO e DF, n=1767) e Nordeste (PE, PB, RN e CE, n=848), coletadas entre 2013 e 2014. Anticorpos neutralizantes contra o VSIV-3 em títulos iguais ou superiores a 40 foram detectados em 641 amostras (17,7%; IC95%: 16,5-19,0%), sendo 317 do CE (positividade de 87,3%; IC95%: 83,4-90,5%); 109 do RN (65,7%; IC95%: 57,8-72,7%); 124 da PB (45,4%; IC95%: 39,4-51,5%); 78 de GO/DF (4,4%; IC95%: 3,5-5,5%) e em nove amostras do RS (0,9%; IC95%: 0,4-1,7%). Uma parcela das amostras dos estados do Nordeste e Centro-oeste apresentou altos títulos neutralizantes, indicando exposição recente ao vírus. Já as amostras do RS apresentaram títulos baixos de anticorpos, indicando provável exposição temporalmente remota. Quando testadas contra outros sorotipos do VSV (Indiana I e New Jersey), várias amostras apresentaram atividade neutralizante, porém em títulos muito inferiores, indicando a especificidade dos anticorpos para o VSIV-3. Esses resultados demonstram circulação relativamente recente do VSIV-3 em várias regiões do Brasil, sobretudo em estados do Nordeste, confirmando relatos clínicos e demonstrando a importância sanitária dessa infecção.

ABSTRACT: Vesicular stomatitis virus (VSV) is the agent of a vesicular disease that affects many animal species and may be clinically confounded with foot-and-mouth disease in ruminant and swine. Horses are especially susceptible to VSV and may serve as sentinels for virus circulation. The present study investigated the presence of neutralizing antibodies against VSV Indiana III (VSIV-3) in serum samples of 3,626 horses from six states in three Brazilian regions: Southern (RS, n = 1,011), Midwest (GO/DF, n = 1,767) and Northeast (PB, PE, RN and CE, n = 848) collected between 2013 and 2014. Neutralizing antibodies against VSIV-3 (titers ≥40) were detected in 641 samples (positivity of 17.7%; CI95%:16.5-19.0%), being 317 samples from CE (87.3%; CI95%: 83.4-90.5 %); 109 from RN (65.7%; CI95%: 57.8 -72.7%); 124 from PB (45.4%; CI95%: 39.4-51.5%); 78 from GO/DF (4.4%; CI95%: 3.5-5.5%) and nine samples of RS (0.9%; CI95%: 0.4-1.7%). Several samples from the Northeast and Midwest harbored high neutralizing titers, indicating a recent exposure to the virus. In contrast, samples from RS had low titers, possibly due to a past remote exposure. Several positive samples presented neutralizing activity against other VSV serotypes (Indiana I and New Jersey), yet in lower titers, indicating the specificity of the response to VSIV-3. These results demonstrated a relatively recent circulation of VSIV-3 in northeastern Brazilian States, confirming clinical findings and demonstrating the sanitary importance of this infection.