ABSTRACT
Herein we evaluated the genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) from Bothrops pauloensis, on breast cancer cells. BnSP-6 was able to induce a higher cytotoxic and genotoxic activity in MDA-MB-231 cells, when compared to MCF10A (a non-tumorigenic breast cell line), suggesting that this protein presented a possible preference for cancer cells. BnSP-6 inhibited MDA-MB-231 proliferation at 24, 48 and 72â¯h. In addition, BnSP-6 induced significant increase in the percentage of TUNEL-positive cells, a marker of DNA damage. To obtain novel insight into the direct DNA damage interference in MDA-MB-231 survival and proliferation, we evaluated cell cycle progression. BnSP-6 produced a significant decrease in 2N (G1) and an increase in the G2/M phase and this capacity is likely related to the modulation of expression of progression cell cycle-associated genes (CCND1, CCNE1, CDC25A, CHEK2, E2F1, CDH-1 and NF-kB). Taken together, these results indicate that BnSP-6 induces DNA damage in breast cancer cells and is an attractive model for developing innovative therapeutic agents against breast cancer.
Subject(s)
Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Crotalid Venoms/pharmacology , Phospholipases A2/pharmacology , Snake Venoms/enzymology , Amino Acid Sequence , Animals , Bothrops/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Crotalid Venoms/chemistry , Crotalid Venoms/genetics , DNA Damage/drug effects , Female , Humans , Lysine/chemistry , Phospholipases A2/chemistry , Phospholipases A2/genetics , Sequence Homology, Amino Acid , Snake Venoms/chemistryABSTRACT
Herein we evaluated the genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) from Bothrops pauloensis, on breast cancer cells. BnSP-6 was able to induce a higher cytotoxic and genotoxic activity in MDA-MB-231 cells, when compared to MCF10A (a non-tumorigenic breast cell line), suggesting that this protein presented a possible preference for cancer cells. BnSP-6 inhibited MDA-MB-231 proliferation at 24, 48 and 72?h. In addition, BnSP-6 induced significant increase in the percentage of TUNEL-positive cells, a marker of DNA damage. To obtain novel insight into the direct DNA damage interference in MDA-MB-231 survival and proliferation, we evaluated cell cycle progression. BnSP-6 produced a significant decrease in 2N (G1) and an increase in the G2/M phase and this capacity is likely related to the modulation of expression of progression cell cycle-associated genes (CCND1, CCNE1, CDC25A, CHEK2, E2F1, CDH-1 and NF-kB). Taken together, these results indicate that BnSP-6 induces DNA damage in breast cancer cells and is an attractive model for developing innovative therapeutic agents against breast cancer.
ABSTRACT
Herein we evaluated the genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) from Bothrops pauloensis, on breast cancer cells. BnSP-6 was able to induce a higher cytotoxic and genotoxic activity in MDA-MB-231 cells, when compared to MCF10A (a non-tumorigenic breast cell line), suggesting that this protein presented a possible preference for cancer cells. BnSP-6 inhibited MDA-MB-231 proliferation at 24, 48 and 72?h. In addition, BnSP-6 induced significant increase in the percentage of TUNEL-positive cells, a marker of DNA damage. To obtain novel insight into the direct DNA damage interference in MDA-MB-231 survival and proliferation, we evaluated cell cycle progression. BnSP-6 produced a significant decrease in 2N (G1) and an increase in the G2/M phase and this capacity is likely related to the modulation of expression of progression cell cycle-associated genes (CCND1, CCNE1, CDC25A, CHEK2, E2F1, CDH-1 and NF-kB). Taken together, these results indicate that BnSP-6 induces DNA damage in breast cancer cells and is an attractive model for developing innovative therapeutic agents against breast cancer.
ABSTRACT
Em face ao aumento do número de processos contra profissionais cirurgiões-dentistas, em especial os ortodontistas, este estudo teve o objetivo de avaliar as decisões dos tribunais em processos contra estes profissionais, mais precisamente no que concerne à natureza da responsabilidade civil de sua obrigação, se "de meio" ou "de resultado". Foi verificada também a proporção do número de processos com ações procedentes e improcedentes, além de conhecer o perfil dos apelantes e apelados. Trata-se de um estudo observacional analítico sobre decisões judiciais que envolveram tratamentos ortodônticos, entre os anos de 2001 a 2011, avaliados nos sites dos tribunais regionais brasileiros utilizando como palavra-chave ortodontia. Somente foi levada em consideração a decisão final em grau recursal, desconsiderando-se a decisão de primeira instância. Os dados foram compilados em Figuras e tabelas por meio de análise descritiva e teste Exato de Fisher (p < 0,001). Na região sudeste concentra-se a maior concentração (45%, n=27) de processos do Brasil, principalmente o estado de São Paulo. Quanto à natureza da obrigação, a de meio foi a mais encontrada (83%, n=50); o número de ações improcedentes (65%) foi maior que ações procedentes. As mulheres foram as principais apelantes (81%, n=49) e as pessoas jurídicas foram a maioria das apeladas (41%, n=24). Foi possível concluir que os tribunais de justiça classificaram a ortodontia como obrigação de meio, e o número de ações improcedentes foram maiores as procedentes. Quando a obrigação é de resultado, a tendência da ação ser procedente é maior. Já, em relação ao perfil dos apelantes (reclamantes), a maioria foi mulheres e, a maioria dos apelados foi pessoas jurídicas.
Given the increased number of lawsuits against dentists, particularly orthodontists, this study aimed to evaluate court decisions regarding lawsuits against these professionals, focusing precisely on the nature of their liability as a "mean" or "result" obligation. Also, it was verified the ratio between the number of lawsuits and founded and unfounded actions, in addition to knowing appellants' and appellees' profile. This is an observational analytical study about court decisions involving orthodontic treatments, between the years 2001 and 2011, evaluated on the Brazilian regional courts websites using the keyword orthodontics. It was taken into account only the final decision upon appeal, disregarding the decision of first instance. Data were compiled into tables and graphs by means of descriptive analysis and Fisher's exact test (P<0.001). Southeast concentrates the majority of lawsuits (45%, n = 27) in Brazil, mostly the state of Sao Paulo. As to the nature of the duty, the obligation of mean was found most frequently (83%, n = 50); and the number of unfounded actions (65%) was greater than founded ones. Women were the main appellants (81%, n = 49), and appellees were mostly legal entities (41%, n = 24). It is concluded that courts of justice have classified orthodontics as an obligation of mean, and the number of unfounded actions was greater than that of founded ones. When it is an obligation of result, the odds for the action to be founded is greater. In relation to the appellants' profile (claimants), the majority was women, and most of the appellees were legal entities.
