RESUMO
Aim: Investigate the apoptotic mechanisms of two new aldehyde biphenyl chalcones on leukemia cells. Materials & methods: From a series of 71 new chalcones, we selected the two most cytotoxic. Results: JA3 and JA7 were cytotoxic not only against hematological malignancies but also against solid tumor and cancer stem cells, yet with no toxicity to normal cells. Moreover, they induced immunogenic apoptotic-like cell death independently of promyelocytic leukemia protein, with extensive mitochondrial damages downstream of endoplasmic reticulum stress. Preventing endoplasmic reticulum stress and the upregulation of proapoptotic machinery inhibited JA3- and JA7-induced cell death. Likewise, blocking receptor Fas protected cells from killing. They increased the antileukemic effect of cytarabine and vincristine and killed leukemic cells collected from patients with different acute leukemia subtypes. Conclusion:JA3 and JA7 represent new promising prototypes for the development of new chemotherapeutics.
Assuntos
Aldeídos/farmacologia , Antineoplásicos/farmacologia , Compostos de Bifenilo/farmacologia , Chalconas/farmacologia , Aldeídos/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chalconas/síntese química , Chalconas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Camundongos , Relação Estrutura-AtividadeRESUMO
Multiparameter flow cytometry is a highly sensitive, fast, and specific diagnostic technology with a wide range of applicability in hematology. Although well-established eight-color immunophenotyping panels are already available, most Brazilian clinical laboratories are equipped with four-color flow cytometer facilities. Based on this fact, the Brazilian Group of Flow Cytometry (Grupo Brasileiro de Citometria de Fluxo, GBCFLUX) for standardization of clinical flow cytometry has proposed an antibody panel designed to allow precise diagnosis and characterization of acute leukemia (AL) within resource-restricted areas. Morphological analysis of bone marrow smears, together with the screening panel, is mandatory for the primary identification of AL. The disease-oriented panels proposed here are divided into three levels of recommendations (mandatory, recommendable, and optional) in order to provide an accurate final diagnosis, as well as allow some degree of flexibility based on available local resources and patient-specific needs. The proposed panels will be subsequently validated in an interlaboratory study to evaluate its effectiveness on the diagnosis and classification of AL. (Assoc editor comm. 2).
Assuntos
Biomarcadores Tumorais/imunologia , Citometria de Fluxo/normas , Imunofenotipagem/normas , Leucemia Mieloide Aguda/diagnóstico , Linfócitos/imunologia , Células Mieloides/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Anticorpos/química , Antígenos CD/genética , Antígenos CD/imunologia , Biomarcadores Tumorais/genética , Brasil , Cor , Análise Citogenética , Citometria de Fluxo/métodos , Corantes Fluorescentes , Humanos , Imunofenotipagem/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Linfócitos/classificação , Linfócitos/patologia , Células Mieloides/classificação , Células Mieloides/patologia , Guias de Prática Clínica como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Multiparameter flow cytometry (MFC) is a highly sensitive, fast and specific diagnostic technology with a wide range of applicability in hematology. Although well-established eight-color immunophenotyping panels are already available, most Brazilian clinical laboratories are equipped with four-color flow cytometer facilities. Based on this fact, the Brazilian Group of Flow Cytometry (Grupo Brasileiro de Citometria de Fluxo, GBCFLUX) for standardization of clinical flow cytometry has proposed an antibody panel designed to allow precise diagnosis and characterization of acute leukemia (AL) within resource-restricted areas. Morphological analysis of bone marrow smears, together with the screening panel, is mandatory for the primary identification of AL. The disease-oriented panels proposed here are divided into three levels of recommendations (mandatory, recommendable and optional) in order to provide an accurate final diagnosis, as well as allow some degree of flexibility based on available local resources and patient-specific needs. The proposed panels will be subsequently validated in an inter-laboratory study to evaluate its effectiveness on the diagnosis and classification of AL. © 2014 Clinical Cytometry Society.
RESUMO
The development of novel xyloglucan-block-poly(ϵ-caprolactone) (XGO-b-PCL) nanoparticles coated with the mucoadhesive polysaccharide chitosan is described. XGO-b-PCL nanoparticles show monodisperse size distribution (Rh = 50 nm). Curcumin is successfully encapsulated within the PCL core within drug to polymer ratio of 1:5 (w/w). The coating of nanoparticles with chitosan results in an increased particle size and positive surface charge due to the polycation nature of the chitosan. Mucoadhesive properties of chitosan-coated nanoparticles are demonstrated by its exceptional ability to interact with mucin through electrostatic forces. Finally, in vitro studies show that curcumin-loaded nanoparticles exhibit higher cytotoxic effects against B16F10 melanoma cells than L929 fibroblast cells.
Assuntos
Adesivos/química , Materiais Biocompatíveis/síntese química , Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Glucanos/química , Nanopartículas/química , Poliésteres/química , Xilanos/química , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Curcumina/administração & dosagem , Curcumina/química , Curcumina/farmacologia , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Modelos Moleculares , Estrutura Molecular , Ressonância de Plasmônio de SuperfícieRESUMO
Curcumin is a polyphenol obtained from the plant Curcuma longa (called turmeric) that displays several pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial and antitumoral activity, but clinical use has been limited by its poor solubility in water and, consequently, minimal systemic bioavailability. We have therefore formulated the drug into nanocarrier systems in an attempt to improve its therapeutic properties. This study evaluates the effect of intraperitoneally administered nanocapsules containing curcumin on subcutaneous melanoma in mice inoculated with B16-F10 cells, and on the cytotoxicity activity against B16-F10 cells in vitro. Phagocytic uptake of formulations was also evaluated upon incubation with macrophage J774 cells by fluorescence microscopy. Lipid and polymeric nanocapsules were prepared by the phase inversion and nanoprecipitation methods, respectively. The uptake of the lipid nanocapsules prepared using Solutol HS15 was significantly reduced in J774 cells. Curcumin, as free drug or as drug-loaded nanocapsules, was administrated at a dose of 6 mg/kg twice a week for 21 days. Free drug and curcumin-loaded nanocapsules significantly reduced tumor volume (P < 0.05 vs. control), but no difference was found in the antitumor activity displayed by lipid and polymeric nanocapsules. This assumption was supported by the in vitro study, in which free curcumin as well as loaded into nanocapsules caused significant reduction of cell viability in a concentration- and time-dependent manner.
Assuntos
Curcumina/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Nanocápsulas , Tensoativos , Animais , Transporte Biológico/efeitos dos fármacos , Linhagem Celular Tumoral , Curcumina/farmacocinética , Curcumina/uso terapêutico , Estabilidade de Medicamentos , Íons , Lipossomos , Macrófagos/imunologia , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Nanocápsulas/química , Tamanho da Partícula , Tensoativos/químicaRESUMO
Gallic acid and gallates with the same number of hydroxyl groups and varying the length of the side carbon chain, with respective lipophilicity being defined through the ClogP values, were examined for their ability to induce apoptosis (through the DNA ladder fragmentation pattern), mitochondrial and cytoplasmic GSH depletion and NF-kappaB activation in murine lymphoblastic L1210 leukemia cells. A relationship between cytotoxic effect and a limited degree of lipophilicity was observed.